Document Information

PMID 16104843  (  )
Title The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions.
Abstract The VEGF (vascular endothelial growth factor) family and its receptors are essential regulators of angiogenesis and vascular permeability. Currently, the VEGF family consists of VEGF-A, PlGF (placenta growth factor), VEGF-B, VEGF-C, VEGF-D, VEGF-E and snake venom VEGF. VEGF-A has at least nine subtypes due to the alternative splicing of a single gene. Although the VEGF165 isoform plays a central role in vascular development, recent studies have demonstrated that each VEGF isoform plays distinct roles in vascular patterning and arterial development. VEGF-A binds to and activates two tyrosine kinase receptors, VEGFR (VEGF receptor)-1 and VEGFR-2. VEGFR-2 mediates most of the endothelial growth and survival signals, but VEGFR-1-mediated signalling plays important roles in pathological conditions such as cancer, ischaemia and inflammation. In solid tumours, VEGF-A and its receptor are involved in carcinogenesis, invasion and distant metastasis as well as tumour angiogenesis. VEGF-A also has a neuroprotective effect on hypoxic motor neurons, and is a modifier of ALS (amyotrophic lateral sclerosis). Recent progress in the molecular and biological understanding of the VEGF/VEGFR system provides us with novel and promising therapeutic strategies and target proteins for overcoming a variety of diseases. 4-6-1 Shirokane-dai, Minato-ku, Tokyo, 108-8639, Japan.

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Targets by SciMiner Summary

HUGO ID Symbol Target Name #Occur ActualStr
12680VEGFAvascular endothelial growth factor A285VEGF-dependent | VEGF-A-like | vegf a | vascular permeability factor | VPF | VEGF-driven | VEGF-A-dependent | VEGF-induced | vascular endothelial growth factor a | VEGF-mediated | VEGFs | VEGF-A-induced |
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)73VEGFR-1-blocking | KDR | VEGFR-2 | Flk-1 | VEGFR-associated | VEGFRs |
8893PGFplacental growth factor38PlGF-2 | plgf 2 | placenta growth factor |
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)37Flt-1 | VEGFR-1 |
8004NRP1neuropilin 123NRP | NRPs | NRP-1 | neuropilin 1 |
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)23vegf d | VEGF-D |
12681VEGFBvascular endothelial growth factor B19VEGF-B |
12682VEGFCvascular endothelial growth factor C19VEGF-C |
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)17HIF-1 | hypoxia inducible factor 1 |
6871MAPK1mitogen-activated protein kinase 116ERK | MAPK-mediated | p38 |
3767FLT4fms-related tyrosine kinase 416Flt-4 | VEGFR-3 |
8005NRP2neuropilin 210neuropilin 2 | NRP-2 |
18420SETD2SET domain containing 29hif 1 |
8975PIK3CAphosphoinositide-3-kinase, catalytic, alpha polypeptide8PI3K | PI3K-dependent |
391AKT1v-akt murine thymoma viral oncogene homolog 14Rac | Akt |
7872NOS1nitric oxide synthase 1 (neuronal)4NOS |
6018IL6interleukin 6 (interferon, beta 2)4IL-6 | il 6 | HGF | interleukin 6 |
10436RPS6KB1ribosomal protein S6 kinase, 70kDa, polypeptide 13p70 s6k | S6K |
9065PLCG1phospholipase C, gamma 13PLC |
7876NOS3nitric oxide synthase 3 (endothelial cell)3eNOS |
7176MMP9matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)3MMP-9 | matrix metalloproteinase 9 | mmp 9 |
3040RCAN1regulator of calcineurin 13DSCR1 |
1764CDH5cadherin 5, type 2, VE-cadherin (vascular epithelium)3ve cadherin |
6206JUNDjun D proto-oncogene3AP-1 | JunD |
18173ERAP1endoplasmic reticulum aminopeptidase 12PILSAP |
11291SRFserum response factor (c-fos serum response element-binding transcription factor)2SRF | serum response factor |
6207JUPjunction plakoglobin2catenin |
5176KRR1KRR1, small subunit (SSU) processome component, homolog (yeast)2rip1 |
8816PDPK13-phosphoinositide dependent protein kinase-12PDK1 |
17970PAIP2poly(A) binding protein interacting protein 22PAIP2 |
15917PLCB1phospholipase C, beta 1 (phosphoinositide-specific)2phospholipase c |
9393PRKCAprotein kinase C, alpha2protein kinase c |
6879MAPK6mitogen-activated protein kinase 62extracellular signal regulated kinase |
9611PTK2PTK2 protein tyrosine kinase 22FAK |
2856DGKQdiacylglycerol kinase, theta 110kDa1diacylglycerol kinase |
21420CCRKcell cycle related kinase1p42 |
13164CNBPCCHC-type zinc finger, nucleic acid binding protein1sterol regulatory element binding protein |
6081INSinsulin1insulin |
10838SHBSrc homology 2 domain containing adaptor protein B1Shb |
12372TSHBthyroid stimulating hormone, beta1thyroid stimulating hormone |
3373EP300E1A binding protein p3001p300 |
9103PLXNB1plexin B11semaphorin receptor |
4893HGFhepatocyte growth factor (hepapoietin A; scatter factor)1hepatocyte growth factor |
8800PDGFBplatelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog)1platelet derived growth factor |
8546P4HA1procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha polypeptide I1prolyl 4 hydroxylase |
1736CDC42cell division cycle 42 (GTP binding protein, 25kDa)1Cdc42 |
16938IFI44interferon-induced protein 441p44 |
2348CREBBPCREB binding protein (Rubinstein-Taybi syndrome)1CBP |
3796FOSv-fos FBJ murine osteosarcoma viral oncogene homolog1ap 1 |
9718PXNpaxillin1paxillin |
7775NFATC1nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 11NFATc |
9106PLXNC1plexin C11plexin |
8607PARK2Parkinson disease (autosomal recessive, juvenile) 2, parkin1e3 ubiquitin ligase |
4281GJA8gap junction protein, alpha 8, 50kDa1cell surface glycoprotein |
1756CDH17cadherin 17, LI cadherin (liver-intestine)1cadherin |
6110IQGAP1IQ motif containing GTPase activating protein 11IQGAP1 |
29884UBASH3Bubiquitin associated and SH3 domain containing, B1p70 |
913AZU1azurocidin 1 (cationic antimicrobial protein 37)1heparin binding protein |
19964VASH1vasohibin 11vasohibin |
2345CREB1cAMP responsive element binding protein 11CREB |
11998TP53tumor protein p531p53 |
8104OCLNoccludin1occludin |
8799PDGFAplatelet-derived growth factor alpha polypeptide1PDGF |
29869SHC2SHC (Src homology 2 domain containing) transforming protein 21Sck |

 

Targets by SciMiner Full list

HUGO ID Symbol Name ActualStr Score FlankingText
12680VEGFAvascular endothelial growth factor AVEGF10.4Foremost among these is the VEGF (vascular vascular endothelial growth factor family and VEGFRs (VEGF VEGF
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFRs3.0is the VEGF (vascular vascular endothelial growth factor family and VEGFRs (VEGF VEGF receptors
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF (vascular vascular endothelial growth factor family and VEGFRs (VEGF VEGF receptors
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A also referred to as VPF (vascular vascular permeability factor an
12680VEGFAvascular endothelial growth factor AVPF5.8VEGF-A also referred to as VPF (vascular vascular permeability factor an important regulator of endothelial cell
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A is a dimeric glycoprotein essential for many angiogenic processes in
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6tumour vascularization mainly by interacting with two tyrosine kinase receptors VEGFR-1 also known as Flt-1 (Fms-like Fms-like tyrosine kinase-1 and VEGFR-2
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)Flt-10.6interacting with two tyrosine kinase receptors VEGFR-1 also known as Flt-1 (Fms-like Fms-like tyrosine kinase-1 and VEGFR-2 also known as Flk-1
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3VEGFR-1 also known as Flt-1 (Fms-like Fms-like tyrosine kinase-1 and VEGFR-2 also known as Flk-1 (fetal fetal liver kinase-1 and in
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)Flk-13.0Flt-1 (Fms-like Fms-like tyrosine kinase-1 and VEGFR-2 also known as Flk-1 (fetal fetal liver kinase-1 and in humans as KDR (kinase
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)KDR3.0as Flk-1 (fetal fetal liver kinase-1 and in humans as KDR (kinase kinase insert domain-containing receptor 3-5
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A exhibits two major biological activities one is the capacity to
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A also promotes the survival and migration of endothelial cells
12680VEGFAvascular endothelial growth factor AVEGF10.4biological functions and the precise molecular mechanisms of the VEGF/VEGFR VEGF VEGFR system
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR3.3functions and the precise molecular mechanisms of the VEGF/VEGFR VEGF VEGFR system
12680VEGFAvascular endothelial growth factor AVEGF10.4the recent advances in the basic biology of the VEGF/VEGFR VEGF VEGFR system which give insight into many physiological and pathological
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR3.3recent advances in the basic biology of the VEGF/VEGFR VEGF VEGFR system which give insight into many physiological and pathological conditions
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF AND VEGF FAMILY PROTEINS
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF AND VEGF FAMILY PROTEINS
12680VEGFAvascular endothelial growth factor AVEGF10.4Currently the VEGF family includes VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Currently the VEGF family includes VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and
8893PGFplacental growth factorPlGF4.6Currently the VEGF family includes VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and svVEGF
12681VEGFBvascular endothelial growth factor BVEGF-B1.8the VEGF family includes VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and svVEGF (snake snake venom VEGF
12682VEGFCvascular endothelial growth factor CVEGF-C1.8VEGF family includes VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and svVEGF (snake snake venom VEGF
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)VEGF-D1.3family includes VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and svVEGF (snake snake venom VEGF
12680VEGFAvascular endothelial growth factor AVEGF10.4factor VEGF-B VEGF-C VEGF-D VEGF-E and svVEGF (snake snake venom VEGF
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A
12680VEGFAvascular endothelial growth factor AVEGF10.4Structurally VEGF belongs to the VEGF/PDGF VEGF PDGF (platelet-derived platelet-derived growth factor
12680VEGFAvascular endothelial growth factor AVEGF10.4Structurally VEGF belongs to the VEGF/PDGF VEGF PDGF (platelet-derived platelet-derived growth factor supergene family
8799PDGFAplatelet-derived growth factor alpha polypeptidePDGF1.2Structurally VEGF belongs to the VEGF/PDGF VEGF PDGF (platelet-derived platelet-derived growth factor supergene family
12680VEGFAvascular endothelial growth factor AVEGF-A7.6The human VEGF-A gene is organized into eight exons separated by seven introns
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Human VEGF-A has at least nine subtypes due to the alternative splicing
12680VEGFAvascular endothelial growth factor AVEGF10.4subtypes due to the alternative splicing of a single gene VEGF 121 VEGF 145 VEGF 148 VEGF 162 VEGF 165 VEGF
12680VEGFAvascular endothelial growth factor AVEGF10.4to the alternative splicing of a single gene VEGF 121 VEGF 145 VEGF 148 VEGF 162 VEGF 165 VEGF 165 b
12680VEGFAvascular endothelial growth factor AVEGF10.4alternative splicing of a single gene VEGF 121 VEGF 145 VEGF 148 VEGF 162 VEGF 165 VEGF 165 b VEGF 183
12680VEGFAvascular endothelial growth factor AVEGF10.4of a single gene VEGF 121 VEGF 145 VEGF 148 VEGF 162 VEGF 165 VEGF 165 b VEGF 183 VEGF 189
12680VEGFAvascular endothelial growth factor AVEGF10.4single gene VEGF 121 VEGF 145 VEGF 148 VEGF 162 VEGF 165 VEGF 165 b VEGF 183 VEGF 189 and VEGF
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF 121 VEGF 145 VEGF 148 VEGF 162 VEGF 165 VEGF 165 b VEGF 183 VEGF 189 and VEGF 206 13
12680VEGFAvascular endothelial growth factor AVEGF10.4145 VEGF 148 VEGF 162 VEGF 165 VEGF 165 b VEGF 183 VEGF 189 and VEGF 206 13 14 ( Figure
12680VEGFAvascular endothelial growth factor AVEGF10.4148 VEGF 162 VEGF 165 VEGF 165 b VEGF 183 VEGF 189 and VEGF 206 13 14 ( Figure 1
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF 165 VEGF 165 b VEGF 183 VEGF 189 and VEGF 206 13 14 ( Figure 1
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF 165 b is an endogenous inhibitory form of VEGF which
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF 165 b is an endogenous inhibitory form of VEGF which binds VEGFR-2 with the same affinity as VEGF 165
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3b is an endogenous inhibitory form of VEGF which binds VEGFR-2 with the same affinity as VEGF 165 but does not
12680VEGFAvascular endothelial growth factor AVEGF10.4of VEGF which binds VEGFR-2 with the same affinity as VEGF 165 but does not activate it or stimulate downstream signalling
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF is produced in endothelial cells macrophages activated T-cells and a
12680VEGFAvascular endothelial growth factor AVEGF10.4Although virtually nothing is known about how VEGF isoform levels are regulated most VEGF-producing cells appear to preferentially
12680VEGFAvascular endothelial growth factor AVEGF10.4levels are regulated most VEGF-producing cells appear to preferentially express VEGF 121 VEGF 165 and VEGF 189
12680VEGFAvascular endothelial growth factor AVEGF10.4regulated most VEGF-producing cells appear to preferentially express VEGF 121 VEGF 165 and VEGF 189
12680VEGFAvascular endothelial growth factor AVEGF10.4cells appear to preferentially express VEGF 121 VEGF 165 and VEGF 189
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF 165 the predominant isoform is secreted as an approx 46
12680VEGFAvascular endothelial growth factor AVEGF10.4In contrast VEGF 121 which lacks the residues encoded by exons 6 and
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF 189 which contains an additional sequence encoded by exon 6
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF 165 binds the coreceptors NRP-1 (neuropilin-1) neuropilin-1 20 and NRP-2
8004NRP1neuropilin 1NRP-10.8VEGF 165 binds the coreceptors NRP-1 (neuropilin-1) neuropilin-1 20 and NRP-2 (neuropilin-2), neuropilin-2 whereas VEGF 145
8005NRP2neuropilin 2NRP-20.3VEGF 165 binds the coreceptors NRP-1 (neuropilin-1) neuropilin-1 20 and NRP-2 (neuropilin-2), neuropilin-2 whereas VEGF 145 binds only NRP-2 21 (
12680VEGFAvascular endothelial growth factor AVEGF10.4coreceptors NRP-1 (neuropilin-1) neuropilin-1 20 and NRP-2 (neuropilin-2), neuropilin-2 whereas VEGF 145 binds only NRP-2 21 ( Figure 2
8005NRP2neuropilin 2NRP-20.320 and NRP-2 (neuropilin-2), neuropilin-2 whereas VEGF 145 binds only NRP-2 21 ( Figure 2
12680VEGFAvascular endothelial growth factor AVEGF10.4Approx 50% of mice expressing exclusively the VEGF 120 isoform (murine murine VEGF is shorter by one amino
12680VEGFAvascular endothelial growth factor AVEGF10.4of mice expressing exclusively the VEGF 120 isoform (murine murine VEGF is shorter by one amino acid die within a few
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF mice also exhibit a specific decrease in capillary branch formation
12680VEGFAvascular endothelial growth factor AVEGF10.4retinal vascular outgrowth and patterning 24 suggesting that the heparin-binding VEGF isoforms provide spatially restricted stimulatory cues to initiate vascular branch
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF mice are normal and healthy and have a normal retinal
12680VEGFAvascular endothelial growth factor AVEGF10.4normal and healthy and have a normal retinal angiogenesis whereas VEGF mice display normal venular outgrowth but impaired arterial development in
12680VEGFAvascular endothelial growth factor AVEGF10.4These findings suggest that the various VEGF isoforms play distinct roles in vascular patterning and arterial development
12680VEGFAvascular endothelial growth factor AVEGF10.4distinct roles in vascular patterning and arterial development although the VEGF 164 isoform plays a central role in vascular development
12680VEGFAvascular endothelial growth factor AVEGF10.4Gene expression of VEGF is regulated by a variety of stimuli such as hypoxia
11998TP53tumor protein p53p530.3a variety of stimuli such as hypoxia growth factors transformation p53 mutation oestrogen TSH (thyroid-stimulating thyroid-stimulating hormone tumour promoters and NO
12680VEGFAvascular endothelial growth factor AVEGF10.4all of the stimuli responsible for the up-regulation of the VEGF gene are quite interesting hypoxia has been of particular interest
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)HIF-10.6It is now well established that HIF-1 (hypoxia-inducible hypoxia-inducible factor-1 is a key mediator of hypoxic responses
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)HIF-10.6HIF-1 is a transcriptional activator composed of HIF-1 a and HIF-1
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)HIF-10.6HIF-1 is a transcriptional activator composed of HIF-1 a and HIF-1 b subunits
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)HIF-10.6HIF-1 is a transcriptional activator composed of HIF-1 a and HIF-1 b subunits
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)HIF-10.6Both HIF-1 a and HIF-1 b are constitutively expressed in various types
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)HIF-10.6Both HIF-1 a and HIF-1 b are constitutively expressed in various types of tumour
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)HIF-10.6Under normal oxygenation conditions HIF-1 a is scarcely detectable because it is targeted for rapid
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)HIF-10.6The interaction between pVHL and a specific domain of the HIF-1 a subunit is regulated through hydroxylation of a proline residue
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)HIF-10.6regulated through hydroxylation of a proline residue (Pro Pro in HIF-1 a by prolyl-4-hydroxylase which requires molecular oxygen and iron for
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)HIF-10.6Under hypoxic conditions HIF-1 a expression increases as a result of suppressed prolyl hydroxylation
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)HIF-10.6expression increases as a result of suppressed prolyl hydroxylation of HIF-1 a and decreased ubiquitination and degradation 26 27
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)HIF-10.6the oxygen-dependent hydroxylation of an asparagine residue (Asn Asn in HIF-1 a in the C-terminal transactivation domain of HIF-1 a to
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)HIF-10.6Asn in HIF-1 a in the C-terminal transactivation domain of HIF-1 a to promote interaction with the p300/CBP p300 CBP CREB
3373EP300E1A binding protein p300p3001.3domain of HIF-1 a to promote interaction with the p300/CBP p300 CBP CREB (cAMP-response-element-binding cAMP-response-element-binding protein -binding protein co-activator and induce
2348CREBBPCREB binding protein (Rubinstein-Taybi syndrome)CBP0.6of HIF-1 a to promote interaction with the p300/CBP p300 CBP CREB (cAMP-response-element-binding cAMP-response-element-binding protein -binding protein co-activator and induce a
2345CREB1cAMP responsive element binding protein 1CREB1.6HIF-1 a to promote interaction with the p300/CBP p300 CBP CREB (cAMP-response-element-binding cAMP-response-element-binding protein -binding protein co-activator and induce a HRE
12680VEGFAvascular endothelial growth factor AVEGF10.4a HRE (hypoxia hypoxia response element -driven transcription of the VEGF gene 28
6206JUNDjun D proto-oncogeneJunD1.5Very recently Gerald et al 29 have demonstrated that JunD a member of the AP-1 family of transcription factors is
6206JUNDjun D proto-oncogeneAP-11.5al 29 have demonstrated that JunD a member of the AP-1 family of transcription factors is involved in the regulation of
6206JUNDjun D proto-oncogeneJunD1.5Deletion of JunD increases H 2 O 2 levels and thus inhibits prolyl
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)HIF-10.6Consequently HIF-1 a protein accumulates under normoxic conditions and the transcription of
12680VEGFAvascular endothelial growth factor AVEGF-A7.6a protein accumulates under normoxic conditions and the transcription of VEGF-A is increased 29
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF is also regulated at the level of mRNA stability
12680VEGFAvascular endothelial growth factor AVEGF10.4The 5_amp_#180;- and 3_amp_#180 -UTRs (untranslated untranslated regions of the VEGF gene confer increased mRNA stability during hypoxia
17970PAIP2poly(A) binding protein interacting protein 2PAIP20.6HuR an AU-rich element binding protein and PAIP2 polyadenylated-binding protein-interacting protein 2 have been identified as crucial proteins
12680VEGFAvascular endothelial growth factor AVEGF10.4protein-interacting protein 2 have been identified as crucial proteins for VEGF mRNA stabilization 30 31
12680VEGFAvascular endothelial growth factor AVEGF10.4Furthermore VEGF expression can be regulated at the translational level
12680VEGFAvascular endothelial growth factor AVEGF10.4It has been shown that the 5_amp_#180 -UTR of VEGF mRNA contains two functional internal ribosome entry sites that maintain
12680VEGFAvascular endothelial growth factor AVEGF10.4that maintain efficient cap-independent translation and ensure efficient production of VEGF even under unfavourable stress conditions such as hypoxia 32
8893PGFplacental growth factorPlGF4.6PlGF
8893PGFplacental growth factorPlGF4.6PlGF was originally discovered in human placenta in 1991 33
8893PGFplacental growth factorPlGF4.6The PlGF gene is highly expressed in placenta at all stages of
8893PGFplacental growth factorPlGF4.6PlGF transcripts have also been detected in the heart lung thyroid
8893PGFplacental growth factorPlGF4.6PlGF binds VEGFR-1 but not VEGFR-2 35 36
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6PlGF binds VEGFR-1 but not VEGFR-2 35 36
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3PlGF binds VEGFR-1 but not VEGFR-2 35 36
8893PGFplacental growth factorPlGF4.6Alternative splicing of the human PlGF gene generates four isoforms which differ in size and binding
8893PGFplacental growth factorPlGF4.6isoforms which differ in size and binding properties PlGF-1 (PlGF PlGF 131 PlGF-2 (PlGF PlGF 152 PlGF-3 (PlGF PlGF 203 and
8893PGFplacental growth factorPlGF-23.1differ in size and binding properties PlGF-1 (PlGF PlGF 131 PlGF-2 (PlGF PlGF 152 PlGF-3 (PlGF PlGF 203 and PlGF-4 (PlGF
8893PGFplacental growth factorPlGF4.6size and binding properties PlGF-1 (PlGF PlGF 131 PlGF-2 (PlGF PlGF 152 PlGF-3 (PlGF PlGF 203 and PlGF-4 (PlGF PlGF 224
8893PGFplacental growth factorPlGF4.6PlGF-1 (PlGF PlGF 131 PlGF-2 (PlGF PlGF 152 PlGF-3 (PlGF PlGF 203 and PlGF-4 (PlGF PlGF 224 37-39 ( Figure 1
8893PGFplacental growth factorPlGF4.6(PlGF PlGF 152 PlGF-3 (PlGF PlGF 203 and PlGF-4 (PlGF PlGF 224 37-39 ( Figure 1
8893PGFplacental growth factorPlGF-23.1PlGF-2 is able to bind heparin and the co-receptors NRP-1 and
8004NRP1neuropilin 1NRP-10.8PlGF-2 is able to bind heparin and the co-receptors NRP-1 and NRP-2 due to the insertion of a highly basic
8005NRP2neuropilin 2NRP-20.3is able to bind heparin and the co-receptors NRP-1 and NRP-2 due to the insertion of a highly basic 21-amino acid
8893PGFplacental growth factorPlGF4.672-amino acid sequence between exons 4 and 5 of the PlGF gene but lacks the coding sequence of exon 6 is
8893PGFplacental growth factorPlGF-23.1a heparin-binding domain previously thought to be present only in PlGF-2 39
12680VEGFAvascular endothelial growth factor AVEGF-A7.6PlGF-1 has shown that this protein is structurally similar to VEGF-A 40
8893PGFplacental growth factorPlGF4.6Furthermore despite this moderate sequence conservation PlGF and VEGF-A bind to the same binding interface of VEGFR-1
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Furthermore despite this moderate sequence conservation PlGF and VEGF-A bind to the same binding interface of VEGFR-1 in a
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6PlGF and VEGF-A bind to the same binding interface of VEGFR-1 in a very similar fashion 41
12680VEGFAvascular endothelial growth factor AVEGF-A7.6However recent studies have reported that unlike in VEGF-A N-glycosylation in PlGF plays an important role in VEGFR-1 binding
8893PGFplacental growth factorPlGF4.6recent studies have reported that unlike in VEGF-A N-glycosylation in PlGF plays an important role in VEGFR-1 binding 42
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6in VEGF-A N-glycosylation in PlGF plays an important role in VEGFR-1 binding 42
8893PGFplacental growth factorPlGF4.6Carmeliet et al 43 have shown that a deficiency in PlGF (PlGF PlGF does not affect embryonic angiogenesis in mice
8893PGFplacental growth factorPlGF4.6al 43 have shown that a deficiency in PlGF (PlGF PlGF does not affect embryonic angiogenesis in mice
8893PGFplacental growth factorPlGF4.6However loss of PlGF impairs angiogenesis plasma extravasation and collateral growth during ischaemia inflammation
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6ischaemia inflammation wound healing and cancer indicating the importance of VEGFR-1 signalling in pathological conditions
12681VEGFBvascular endothelial growth factor BVEGF-B1.8VEGF-B
12681VEGFBvascular endothelial growth factor BVEGF-B1.8VEGF-B has a wide tissue distribution but is particularly abundant in
12681VEGFBvascular endothelial growth factor BVEGF-B1.8Human VEGF-B has two isoforms generated by alternative splicing VEGF-B 167 and
12681VEGFBvascular endothelial growth factor BVEGF-B1.8Human VEGF-B has two isoforms generated by alternative splicing VEGF-B 167 and VEGF-B 186 ( Figure 1
12681VEGFBvascular endothelial growth factor BVEGF-B1.8has two isoforms generated by alternative splicing VEGF-B 167 and VEGF-B 186 ( Figure 1
12681VEGFBvascular endothelial growth factor BVEGF-B1.8The VEGF-B isoforms bind and activate VEGFR-1 and can also bind to
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6The VEGF-B isoforms bind and activate VEGFR-1 and can also bind to NRP-1 44 ( Figure 2
8004NRP1neuropilin 1NRP-10.8isoforms bind and activate VEGFR-1 and can also bind to NRP-1 44 ( Figure 2
12681VEGFBvascular endothelial growth factor BVEGF-B1.8Studies using VEGF-B knockout (VEGF-B VEGF-B mice have yielded slightly conflicting results regarding
12681VEGFBvascular endothelial growth factor BVEGF-B1.8Studies using VEGF-B knockout (VEGF-B VEGF-B mice have yielded slightly conflicting results regarding the role of
12681VEGFBvascular endothelial growth factor BVEGF-B1.8mice have yielded slightly conflicting results regarding the role of VEGF-B in angiogenesis and the development of the cardiovascular system
12681VEGFBvascular endothelial growth factor BVEGF-B1.8VEGF-B mice are viable and fertile however although Bellomo et al
12681VEGFBvascular endothelial growth factor BVEGF-B1.8and fertile however although Bellomo et al 45 demonstrated that VEGF-B mice had smaller hearts dysfunctional coronary arteries and an impaired
12681VEGFBvascular endothelial growth factor BVEGF-B1.8conduction abnormality characterized by a prolonged PQ interval and that VEGF-B was not required for proper development of the cardiovascular system
12681VEGFBvascular endothelial growth factor BVEGF-B1.8Recent studies using VEGF-B mice have demonstrated the role of VEGF-B in pathological vascular
12681VEGFBvascular endothelial growth factor BVEGF-B1.8Recent studies using VEGF-B mice have demonstrated the role of VEGF-B in pathological vascular remodelling in inflammatory arthritis 47 and protection
12682VEGFCvascular endothelial growth factor CVEGF-C1.8VEGF-C and VEGF-D
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)VEGF-D1.3VEGF-C and VEGF-D
12682VEGFCvascular endothelial growth factor CVEGF-C1.8VEGF-C contains a region sharing approx 30% amino acid identity with
12680VEGFAvascular endothelial growth factor AVEGF10.4contains a region sharing approx 30% amino acid identity with VEGF 165 however it is more closely related to VEGF-D by
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)VEGF-D1.3with VEGF 165 however it is more closely related to VEGF-D by virtue of the presence of N- and C-terminal extensions
12680VEGFAvascular endothelial growth factor AVEGF10.4N- and C-terminal extensions that are not found in other VEGF family members 49 ( Figure 1
12682VEGFCvascular endothelial growth factor CVEGF-C1.8Both VEGF-C and VEGF-D bind and activate VEGFR-3 (Flt-4; Flt-4 a member
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)VEGF-D1.3Both VEGF-C and VEGF-D bind and activate VEGFR-3 (Flt-4; Flt-4 a member of the
3767FLT4fms-related tyrosine kinase 4VEGFR-30.6Both VEGF-C and VEGF-D bind and activate VEGFR-3 (Flt-4; Flt-4 a member of the VEGFR family that does
3767FLT4fms-related tyrosine kinase 4Flt-40.6Both VEGF-C and VEGF-D bind and activate VEGFR-3 (Flt-4; Flt-4 a member of the VEGFR family that does not bind
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR3.3bind and activate VEGFR-3 (Flt-4; Flt-4 a member of the VEGFR family that does not bind VEGF-A as well as VEGFR-2
12680VEGFAvascular endothelial growth factor AVEGF-A7.6a member of the VEGFR family that does not bind VEGF-A as well as VEGFR-2 and are mitogenic for cultured endothelial
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3VEGFR family that does not bind VEGF-A as well as VEGFR-2 and are mitogenic for cultured endothelial cells
12682VEGFCvascular endothelial growth factor CVEGF-C1.8VEGF-C also binds to NRP-2 49 ( Figure 2
8005NRP2neuropilin 2NRP-20.3VEGF-C also binds to NRP-2 49 ( Figure 2
12682VEGFCvascular endothelial growth factor CVEGF-C1.8Both VEGF-C and VEGF-D are produced as a preproprotein with long N-
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)VEGF-D1.3Both VEGF-C and VEGF-D are produced as a preproprotein with long N- and C-terminal
12680VEGFAvascular endothelial growth factor AVEGF10.4a preproprotein with long N- and C-terminal propeptides flanking the VEGF homology domain
3767FLT4fms-related tyrosine kinase 4VEGFR-30.6the precursor generates a form with a moderate affinity for VEGFR-3 but a second proteolytic step is required to produce the
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3the fully processed form with a high affinity for both VEGFR-2 and VEGFR-3 49
3767FLT4fms-related tyrosine kinase 4VEGFR-30.6processed form with a high affinity for both VEGFR-2 and VEGFR-3 49
12682VEGFCvascular endothelial growth factor CVEGF-C1.8This activation of VEGF-C and VEGF-D by proteolytic cleavage is at least partly regulated
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)VEGF-D1.3This activation of VEGF-C and VEGF-D by proteolytic cleavage is at least partly regulated by the
12682VEGFCvascular endothelial growth factor CVEGF-C1.8Overexpression of VEGF-C in the epidermis of transgenic mice results in the development
12682VEGFCvascular endothelial growth factor CVEGF-C1.8In vitro VEGF-C and VEGF-D stimulate the migration and mitogenesis of cultured endothelial
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)VEGF-D1.3In vitro VEGF-C and VEGF-D stimulate the migration and mitogenesis of cultured endothelial cells 49
12682VEGFCvascular endothelial growth factor CVEGF-C1.8A recent study using VEGF-C mice has demonstrated that VEGF-C is required for the initial
12682VEGFCvascular endothelial growth factor CVEGF-C1.8A recent study using VEGF-C mice has demonstrated that VEGF-C is required for the initial steps in lymphatic development and
12682VEGFCvascular endothelial growth factor CVEGF-C1.8for the initial steps in lymphatic development and that both VEGF-C alleles are required for normal lymphatic development 52
12682VEGFCvascular endothelial growth factor CVEGF-C1.8Thus VEGF-C is the paracrine factor essential for lymphangiogenesis
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)VEGF-D1.3Less is known of the function of VEGF-D but Stacker et al 53 have revealed that VEGF-D induces
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)VEGF-D1.3of VEGF-D but Stacker et al 53 have revealed that VEGF-D induces the formation of lymphatics within tumours and promotes the
12680VEGFAvascular endothelial growth factor AVEGF10.4Homologues of VEGF have also been identified in the genome of the parapoxvirus
12680VEGFAvascular endothelial growth factor AVEGF-A-like5.8parapoxvirus Orf virus 54 and have been shown to have VEGF-A-like activities
12680VEGFAvascular endothelial growth factor AVEGF10.4for a group of these proteins including VEGF-E NZ-2 (VEGF VEGF from Orf virus strain NZ-2 55 VEGF-E NZ-7 (VEGF VEGF
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF from Orf virus strain NZ-2 55 VEGF-E NZ-7 (VEGF VEGF from Orf virus strain NZ-7 56 VEGF-E NZ-10 (VEGF VEGF
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF from Orf virus strain NZ-7 56 VEGF-E NZ-10 (VEGF VEGF from Orf virus strain NZ-10 57 VEGF-E D1701 (VEGF VEGF
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF from Orf virus strain NZ-10 57 VEGF-E D1701 (VEGF VEGF from Orf virus strain D1701 58 and VEGF-E VR634 (VEGF
12680VEGFAvascular endothelial growth factor AVEGF10.4from Orf virus strain D1701 58 and VEGF-E VR634 (VEGF VEGF from Pseudocowpox virus strain VR634 57
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3All VEGF-E variants studied bind and activate VEGFR-2 but not VEGFR-1 or VEGFR-3
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6All VEGF-E variants studied bind and activate VEGFR-2 but not VEGFR-1 or VEGFR-3
3767FLT4fms-related tyrosine kinase 4VEGFR-30.6variants studied bind and activate VEGFR-2 but not VEGFR-1 or VEGFR-3
8004NRP1neuropilin 1NRP-10.8VEGF-E NZ-2 VEGF-E NZ-10 and VEGF-E D1701 can bind NRP-1
8004NRP1neuropilin 1NRP-10.8VEGF-E NZ-7 and VEGF-E VR634 however are unable to bind NRP-1 ( Figure 2
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF-E seems to be as potent as VEGF 165 at stimulating endothelial cell proliferation despite lacking a heparin-binding
12680VEGFAvascular endothelial growth factor AVEGF10.4Recently VEGF family proteins have been identified in snake venom including svVEGF
12680VEGFAvascular endothelial growth factor AVEGFs5.8et al 61 have shown that snakes utilize these venom-specific VEGFs in addition to VEGF-A svVEGFs function as dimers and each
12680VEGFAvascular endothelial growth factor AVEGF-A7.6shown that snakes utilize these venom-specific VEGFs in addition to VEGF-A svVEGFs function as dimers and each chain comprises approx 110-122
12680VEGFAvascular endothelial growth factor AVEGF10.4The cysteine knot motif a characteristic of the VEGF family of proteins is completely conserved in svVEGFs and the
12680VEGFAvascular endothelial growth factor AVEGF10.4completely conserved in svVEGFs and the sequence identity with human VEGF 165 is approx 50% ( Figure 1
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6Vammin does not bind VEGFR-1 but binds VEGFR-2 with high affinity as well as VEGF
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3Vammin does not bind VEGFR-1 but binds VEGFR-2 with high affinity as well as VEGF 165 64
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGFR-1 but binds VEGFR-2 with high affinity as well as VEGF 165 64
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6However Tf svVEGF binds VEGFR-1 with high affinity and VEGFR-2 with low affinity compared with
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3However Tf svVEGF binds VEGFR-1 with high affinity and VEGFR-2 with low affinity compared with VEGF 165 leading to a
12680VEGFAvascular endothelial growth factor AVEGF10.4with high affinity and VEGFR-2 with low affinity compared with VEGF 165 leading to a strong enhancement of vascular permeability but
3767FLT4fms-related tyrosine kinase 4VEGFR-30.6Both vammin and Tf svVEGF are unable to bind VEGFR-3 or NRP-1 but Tf svVEGF binds heparin svVEGFs may contribute
8004NRP1neuropilin 1NRP-10.8vammin and Tf svVEGF are unable to bind VEGFR-3 or NRP-1 but Tf svVEGF binds heparin svVEGFs may contribute to the
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFRs3.0VEGFRs
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6VEGFR-1
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6VEGFR-1 is a 180 kDa high-affinity receptor for VEGF-A VEGF-B PlGF
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGFR-1 is a 180 kDa high-affinity receptor for VEGF-A VEGF-B PlGF and Tf svVEGF
12681VEGFBvascular endothelial growth factor BVEGF-B1.8VEGFR-1 is a 180 kDa high-affinity receptor for VEGF-A VEGF-B PlGF and Tf svVEGF
8893PGFplacental growth factorPlGF4.6VEGFR-1 is a 180 kDa high-affinity receptor for VEGF-A VEGF-B PlGF and Tf svVEGF
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6The second Ig domain of VEGFR-1 is the major binding site for VEGF-A and PlGF 16
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Ig domain of VEGFR-1 is the major binding site for VEGF-A and PlGF 16 41 67
8893PGFplacental growth factorPlGF4.6of VEGFR-1 is the major binding site for VEGF-A and PlGF 16 41 67
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6VEGFR-1 binds VEGF-A with at least 10-fold higher affinity than VEGFR-2
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGFR-1 binds VEGF-A with at least 10-fold higher affinity than VEGFR-2 ( K
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3VEGFR-1 binds VEGF-A with at least 10-fold higher affinity than VEGFR-2 ( K d =10-30 pM 16 however ligand binding results
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3In many cases the effects of VEGFR-2 on endothelial cells such as those on cell survival and
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6VEGFR-1 is a negative regulator of angiogenesis during early development but
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-1-blocking3.0VEGFR-1-blocking antibodies prevent the migration but not proliferation of HUVECs (human
12680VEGFAvascular endothelial growth factor AVEGF-A7.6HUVECs (human human umbilical vein endothelial cells in response to VEGF-A indicating the involvement of VEGFR-1 in endothelial cell migration 68
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6endothelial cells in response to VEGF-A indicating the involvement of VEGFR-1 in endothelial cell migration 68
6871MAPK1mitogen-activated protein kinase 1p382.2signalling appears to preferentially modulate the reorganization of actin via p38 MAPK (mitogen-activated mitogen-activated protein kinase whereas VEGFR-2 contributes to the
6871MAPK1mitogen-activated protein kinase 1MAPK2.2appears to preferentially modulate the reorganization of actin via p38 MAPK (mitogen-activated mitogen-activated protein kinase whereas VEGFR-2 contributes to the re-organization
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3of actin via p38 MAPK (mitogen-activated mitogen-activated protein kinase whereas VEGFR-2 contributes to the re-organization of the cytoskeleton by phosphorylating FAK
9611PTK2PTK2 protein tyrosine kinase 2FAK0.3VEGFR-2 contributes to the re-organization of the cytoskeleton by phosphorylating FAK (focal focal adhesion kinase and paxillin ( Figure 2 suggesting
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6VEGFR-1 signalling is also involved in the migration of monocytes/macrophages monocytes
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6An alternatively spliced form of VEGFR-1 that encodes a soluble truncated form of the receptor containing
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6cloned from a HUVEC cDNA library 16 sVEGFR-1 (soluble soluble VEGFR-1 inhibits VEGF-A activity by sequestering VEGF-A from signalling receptors and
12680VEGFAvascular endothelial growth factor AVEGF-A7.6a HUVEC cDNA library 16 sVEGFR-1 (soluble soluble VEGFR-1 inhibits VEGF-A activity by sequestering VEGF-A from signalling receptors and by forming
12680VEGFAvascular endothelial growth factor AVEGF-A7.616 sVEGFR-1 (soluble soluble VEGFR-1 inhibits VEGF-A activity by sequestering VEGF-A from signalling receptors and by forming non-signalling heterodimers with VEGFR-2
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3VEGF-A from signalling receptors and by forming non-signalling heterodimers with VEGFR-2 69
12680VEGFAvascular endothelial growth factor AVEGF10.4with pre-eclampsia are associated with decreased circulating levels of free VEGF and PlGF resulting in general endothelial dysfunction 73
8893PGFplacental growth factorPlGF4.6are associated with decreased circulating levels of free VEGF and PlGF resulting in general endothelial dysfunction 73
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3VEGFR-2
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3VEGFR-2 is a 200-230 kDa high-affinity receptor for VEGF-A ( K
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGFR-2 is a 200-230 kDa high-affinity receptor for VEGF-A ( K d =75-760 pM VEGF-E and svVEGFs as well
12682VEGFCvascular endothelial growth factor CVEGF-C1.8VEGF-E and svVEGFs as well as the processed form of VEGF-C and VEGF-D
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)VEGF-D1.3svVEGFs as well as the processed form of VEGF-C and VEGF-D
12680VEGFAvascular endothelial growth factor AVEGF-A7.6The binding site for VEGF-A has been mapped to the second and third Ig domains
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3VEGFR-2 is expressed in vascular and lymphatic endothelial cells and other
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3Tyrosine phosphorylation sites in human VEGFR-2 bound to VEGF-A are Tyr and Tyr in the kinase-insert
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Tyrosine phosphorylation sites in human VEGFR-2 bound to VEGF-A are Tyr and Tyr in the kinase-insert domain Tyr and
12680VEGFAvascular endothelial growth factor AVEGF-A-dependent5.8Among them Tyr and Tyr are the two major VEGF-A-dependent autophosphorylation sites 76
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-associated3.5Tyr creates a binding site for the VEGFR-associated protein 77 and Tyr creates a binding site for Sck
29869SHC2SHC (Src homology 2 domain containing) transforming protein 2Sck0.6VEGFR-associated protein 77 and Tyr creates a binding site for Sck 78 Shb 79 and PLC (phospholipase phospholipase C -g 76
10838SHBSrc homology 2 domain containing adaptor protein BShb0.677 and Tyr creates a binding site for Sck 78 Shb 79 and PLC (phospholipase phospholipase C -g 76
9065PLCG1phospholipase C, gamma 1PLC0.9creates a binding site for Sck 78 Shb 79 and PLC (phospholipase phospholipase C -g 76
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3VEGFR-2 is the major mediator of the mitogenic angiogenic and permeability-enhancing
12680VEGFAvascular endothelial growth factor AVEGF-A7.6major mediator of the mitogenic angiogenic and permeability-enhancing effects of VEGF-A
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3Furthermore recent studies have indicated that the activation of VEGFR-2 also promotes lymphangiogenesis 80 81
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3Survival signalling for endothelial cells from VEGFR-2 is reported to involve the PI3K (phosphoinositide phosphoinositide 3-kinase)/Akt 3-kinase
8975PIK3CAphosphoinositide-3-kinase, catalytic, alpha polypeptidePI3K1.0for endothelial cells from VEGFR-2 is reported to involve the PI3K (phosphoinositide phosphoinositide 3-kinase)/Akt 3-kinase Akt pathway 82 83 ( Figure
391AKT1v-akt murine thymoma viral oncogene homolog 1Akt0.3is reported to involve the PI3K (phosphoinositide phosphoinositide 3-kinase)/Akt 3-kinase Akt pathway 82 83 ( Figure 2
8975PIK3CAphosphoinositide-3-kinase, catalytic, alpha polypeptidePI3K1.0another pathway may be involved since the signal to activate PI3K by VEGFR-2 is usually not very strong
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3may be involved since the signal to activate PI3K by VEGFR-2 is usually not very strong
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3Byzova et al 84 have reported that the activation of VEGFR-2 by VEGF-A results in the PI3K/Akt-dependent PI3K Akt-dependent activation of
12680VEGFAvascular endothelial growth factor AVEGF-A7.6al 84 have reported that the activation of VEGFR-2 by VEGF-A results in the PI3K/Akt-dependent PI3K Akt-dependent activation of several integrins
8975PIK3CAphosphoinositide-3-kinase, catalytic, alpha polypeptidePI3K1.0the activation of VEGFR-2 by VEGF-A results in the PI3K/Akt-dependent PI3K Akt-dependent activation of several integrins leading to enhanced cell adhesion
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3synergic interaction with integrins is required for productive signalling from VEGFR-2
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3Very recently a naturally occurring soluble truncated form of VEGFR-2 has been detected in mouse and human plasma 85
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3Similar to sVEGFR-1 sVEGFR-2 (soluble soluble VEGFR-2 may have regulatory consequences with respect to VEGF-mediated angiogenesis
12680VEGFAvascular endothelial growth factor AVEGF-mediated5.8(soluble soluble VEGFR-2 may have regulatory consequences with respect to VEGF-mediated angiogenesis
3767FLT4fms-related tyrosine kinase 4VEGFR-30.6VEGFR-3
3767FLT4fms-related tyrosine kinase 4VEGFR-30.6VEGFR-3 is a 195 kDa high-affinity receptor for VEGF-C and VEGF-D
12682VEGFCvascular endothelial growth factor CVEGF-C1.8VEGFR-3 is a 195 kDa high-affinity receptor for VEGF-C and VEGF-D
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)VEGF-D1.3VEGFR-3 is a 195 kDa high-affinity receptor for VEGF-C and VEGF-D
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6Unlike VEGFR-1 and VEGFR-2 VEGFR-3 is proteolytically cleaved within the fifth extracellular
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3Unlike VEGFR-1 and VEGFR-2 VEGFR-3 is proteolytically cleaved within the fifth extracellular Ig loop
3767FLT4fms-related tyrosine kinase 4VEGFR-30.6Unlike VEGFR-1 and VEGFR-2 VEGFR-3 is proteolytically cleaved within the fifth extracellular Ig loop into
3767FLT4fms-related tyrosine kinase 4VEGFR-30.6Overexpression of a soluble VEGFR-3 in the skin of mice inhibits fetal lymphangiogenesis and induces
12682VEGFCvascular endothelial growth factor CVEGF-C1.8Furthermore overexpression of a VEGFR-3-specific mutant of VEGF-C (VEGF-C VEGF-C 156S in the skin induces the growth of
12682VEGFCvascular endothelial growth factor CVEGF-C1.8Furthermore overexpression of a VEGFR-3-specific mutant of VEGF-C (VEGF-C VEGF-C 156S in the skin induces the growth of lymphatic vessels
3767FLT4fms-related tyrosine kinase 4VEGFR-30.6on the blood vessel architecture 87 indicating that stimulation of VEGFR-3 alone is sufficient to induce lymphangiogenesis
3767FLT4fms-related tyrosine kinase 4VEGFR-30.6The stimulation of VEGFR-3 also protects the lymphatic endothelial cells from serum deprivation-induced apoptosis
3767FLT4fms-related tyrosine kinase 4VEGFR-30.6The phosphorylation of VEGFR-3 has been shown to lead to a PI3K-dependent activation of
8975PIK3CAphosphoinositide-3-kinase, catalytic, alpha polypeptidePI3K-dependent1.0phosphorylation of VEGFR-3 has been shown to lead to a PI3K-dependent activation of Akt and PKC (protein protein kinase C -dependent
391AKT1v-akt murine thymoma viral oncogene homolog 1Akt0.3has been shown to lead to a PI3K-dependent activation of Akt and PKC (protein protein kinase C -dependent activation of p42/p44
21420CCRKcell cycle related kinasep420.3and PKC (protein protein kinase C -dependent activation of p42/p44 p42 p44 MAPK 88
6871MAPK1mitogen-activated protein kinase 1MAPK2.2(protein protein kinase C -dependent activation of p42/p44 p42 p44 MAPK 88
16938IFI44interferon-induced protein 44p440.5PKC (protein protein kinase C -dependent activation of p42/p44 p42 p44 MAPK 88
3767FLT4fms-related tyrosine kinase 4VEGFR-30.6A recent study 89 has demonstrated that blockade of VEGFR-3 signalling significantly suppresses corneal dendritic cell trafficking to draining lymph
3767FLT4fms-related tyrosine kinase 4VEGFR-30.6hypersensitivity and rejection of corneal transplants suggesting a role for VEGFR-3 in adaptive immunity
8004NRP1neuropilin 1NRP-10.8NRP-1 and NRP-2
8005NRP2neuropilin 2NRP-20.3NRP-1 and NRP-2
8004NRP1neuropilin 1NRP-10.8NRP-1 is a 130-140 kDa cell-surface glycoprotein first identified as a
12680VEGFAvascular endothelial growth factor AVEGF-A7.6guidance 90 and subsequently found as an isoform-specific receptor for VEGF-A 20
8005NRP2neuropilin 2NRP-20.3NRP-2 was identified by virtue of its sequence homology with NRP-1
8004NRP1neuropilin 1NRP-10.8NRP-2 was identified by virtue of its sequence homology with NRP-1 and shares 44% identity at the amino acid level with
8004NRP1neuropilin 1NRP-10.8and shares 44% identity at the amino acid level with NRP-1 90
8004NRP1neuropilin 1NRP-10.8NRP-1 is able to bind VEGF 165 VEGF-B PlGF-2 and some
12680VEGFAvascular endothelial growth factor AVEGF10.4NRP-1 is able to bind VEGF 165 VEGF-B PlGF-2 and some VEGF-E variants whereas NRP-2 can
12681VEGFBvascular endothelial growth factor BVEGF-B1.8NRP-1 is able to bind VEGF 165 VEGF-B PlGF-2 and some VEGF-E variants whereas NRP-2 can bind VEGF
8893PGFplacental growth factorPlGF-23.1NRP-1 is able to bind VEGF 165 VEGF-B PlGF-2 and some VEGF-E variants whereas NRP-2 can bind VEGF 145
8005NRP2neuropilin 2NRP-20.3bind VEGF 165 VEGF-B PlGF-2 and some VEGF-E variants whereas NRP-2 can bind VEGF 145 VEGF 165 PlGF-2 and VEGF-C
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF-B PlGF-2 and some VEGF-E variants whereas NRP-2 can bind VEGF 145 VEGF 165 PlGF-2 and VEGF-C
12680VEGFAvascular endothelial growth factor AVEGF10.4and some VEGF-E variants whereas NRP-2 can bind VEGF 145 VEGF 165 PlGF-2 and VEGF-C
8893PGFplacental growth factorPlGF-23.1VEGF-E variants whereas NRP-2 can bind VEGF 145 VEGF 165 PlGF-2 and VEGF-C
12682VEGFCvascular endothelial growth factor CVEGF-C1.8whereas NRP-2 can bind VEGF 145 VEGF 165 PlGF-2 and VEGF-C
8004NRP1neuropilin 1NRPs0.8The intracellular domains of NRPs are short and do not suffice for the independent transduction
12680VEGFAvascular endothelial growth factor AVEGF10.4the independent transduction of biological signals subsequent to semaphorin or VEGF binding
8004NRP1neuropilin 1NRPs0.8It has been shown that both NRPs can join with receptors belonging to the plexin family and
8004NRP1neuropilin 1NRP0.8receptors belonging to the plexin family and such plexin/NRP plexin NRP complexes are able to transduce signals as the physiological receptor
12680VEGFAvascular endothelial growth factor AVEGF10.4The VEGF 165 -induced proliferation and migration of cells that express VEGFR-2
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3VEGF 165 -induced proliferation and migration of cells that express VEGFR-2 are enhanced in the presence of NRP-1
8004NRP1neuropilin 1NRP-10.8cells that express VEGFR-2 are enhanced in the presence of NRP-1
8004NRP1neuropilin 1NRP-10.8Thus NRP-1 also seems to function as an enhancer of VEGFR-2 activity
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3Thus NRP-1 also seems to function as an enhancer of VEGFR-2 activity in the presence of VEGF 165
12680VEGFAvascular endothelial growth factor AVEGF10.4as an enhancer of VEGFR-2 activity in the presence of VEGF 165
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3is the result of the formation of a complex between VEGFR-2 and NRP-1 93 94
8004NRP1neuropilin 1NRP-10.8result of the formation of a complex between VEGFR-2 and NRP-1 93 94
8004NRP1neuropilin 1NRP-10.8An in vivo study with transgenic mice has shown that NRP-1 is important not only for neuronal development but also for
8004NRP1neuropilin 1NRP-10.8NRP-1 mice suffer from severe defects in the cardiovascular system in
8004NRP1neuropilin 1NRP-10.8aortic arches and the yolk-sac vasculature suggesting the importance of NRP-1 in embryonic vessel formation
8005NRP2neuropilin 2NRP-20.3In contrast NRP-2 mice show an absence or severe reduction of small lymphatic
8005NRP2neuropilin 2NRP-20.3veins and larger collecting lymphatic vessels develop normally suggesting that NRP-2 is selectively required for the formation of small lymphatic vessels
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF/VEGFR VEGF VEGFR SYSTEM IN PHYSIOLOGICAL AND PATHOLOGICAL CONDITIONS
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR3.3VEGF/VEGFR VEGF VEGFR SYSTEM IN PHYSIOLOGICAL AND PATHOLOGICAL CONDITIONS
12680VEGFAvascular endothelial growth factor AVEGF10.4The loss of a single VEGF allele is lethal in the mouse embryo between days 11
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF embryos exhibit significant defects in the vasculature of several organs
12680VEGFAvascular endothelial growth factor AVEGF-A7.6In addition a 2- to 3-fold overexpression of VEGF-A from its endogenous locus results in severe abnormalities in heart
12680VEGFAvascular endothelial growth factor AVEGF-A7.6These results demonstrate the importance of tightly regulating VEGF-A expression during embryonic development
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6Homozygous loss of the VEGFR-1 or VEGFR-2 gene results in embryonic lethality between days 8.5
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3Homozygous loss of the VEGFR-1 or VEGFR-2 gene results in embryonic lethality between days 8.5 and 9.5
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFRs3.0embryonic lethality between days 8.5 and 9.5 indicating that these VEGFRs play important roles in vasculogenesis and angiogenesis 101 102
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3VEGFR-2 mice die due to a lack of endothelial cell growth
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6On the other hand VEGFR-1 mice die due to an overgrowth of endothelial cells and
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6vascular development in mice lacking the tyrosine kinase domain of VEGFR-1 103 has indicated that VEGFR-2 is the major positive signal
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3the tyrosine kinase domain of VEGFR-1 103 has indicated that VEGFR-2 is the major positive signal transducer whereas VEGFR-1 has a
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6indicated that VEGFR-2 is the major positive signal transducer whereas VEGFR-1 has a negative regulatory role in angiogenesis early in embryogenesis
12680VEGFAvascular endothelial growth factor AVEGF-A-dependent5.876 have shown that Tyr and Tyr are two major VEGF-A-dependent autophosphorylation sites in VEGFR-2
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3Tyr and Tyr are two major VEGF-A-dependent autophosphorylation sites in VEGFR-2
12680VEGFAvascular endothelial growth factor AVEGF-dependent5.8However only autophosphorylation of Tyr is crucial for VEGF-dependent endothelial cell proliferation via the PLC-g /PKC/Raf/MEK PKC Raf MEK
6871MAPK1mitogen-activated protein kinase 1MAPK2.2cell proliferation via the PLC-g /PKC/Raf/MEK PKC Raf MEK [MAPK/ERK MAPK ERK (extracellular-signal-regulated extracellular-signal-regulated kinase kinase]/ERK kinase ERK pathway
6871MAPK1mitogen-activated protein kinase 1ERK2.2proliferation via the PLC-g /PKC/Raf/MEK PKC Raf MEK [MAPK/ERK MAPK ERK (extracellular-signal-regulated extracellular-signal-regulated kinase kinase]/ERK kinase ERK pathway
6871MAPK1mitogen-activated protein kinase 1ERK2.2Raf MEK [MAPK/ERK MAPK ERK (extracellular-signal-regulated extracellular-signal-regulated kinase kinase]/ERK kinase ERK pathway
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3An unusual feature of mitogenic signalling from VEGFR-2 is the requirement for PKC but not Ras 104
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3knockin mice substituting Tyr (corresponding corresponding to Tyr in human VEGFR-2 and Tyr (Tyr Tyr in human of the VEGFR-2 gene
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3human VEGFR-2 and Tyr (Tyr Tyr in human of the VEGFR-2 gene with phenylalanine has revealed that the signalling via Tyr
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3with phenylalanine has revealed that the signalling via Tyr of VEGFR-2 is essential for endothelial and haematopoietic development during embryogenesis
1736CDC42cell division cycle 42 (GTP binding protein, 25kDa)Cdc420.3appears to be required to trigger the sequential activation of Cdc42 and p38 MAPK and to drive p38 MAPK-mediated actin remodelling
6871MAPK1mitogen-activated protein kinase 1p382.2be required to trigger the sequential activation of Cdc42 and p38 MAPK and to drive p38 MAPK-mediated actin remodelling in stress
6871MAPK1mitogen-activated protein kinase 1MAPK2.2required to trigger the sequential activation of Cdc42 and p38 MAPK and to drive p38 MAPK-mediated actin remodelling in stress fibres
6871MAPK1mitogen-activated protein kinase 1p382.2sequential activation of Cdc42 and p38 MAPK and to drive p38 MAPK-mediated actin remodelling in stress fibres in endothelial cells exposed
6871MAPK1mitogen-activated protein kinase 1MAPK-mediated2.2activation of Cdc42 and p38 MAPK and to drive p38 MAPK-mediated actin remodelling in stress fibres in endothelial cells exposed to
12680VEGFAvascular endothelial growth factor AVEGF-A7.6actin remodelling in stress fibres in endothelial cells exposed to VEGF-A 106
8975PIK3CAphosphoinositide-3-kinase, catalytic, alpha polypeptidePI3K1.0The activation of the PI3K/p70 PI3K p70 S6K (S6 S6 kinase pathway by VEGFR-2 is also
29884UBASH3Bubiquitin associated and SH3 domain containing, Bp700.6The activation of the PI3K/p70 PI3K p70 S6K (S6 S6 kinase pathway by VEGFR-2 is also involved
10436RPS6KB1ribosomal protein S6 kinase, 70kDa, polypeptide 1S6K1.0The activation of the PI3K/p70 PI3K p70 S6K (S6 S6 kinase pathway by VEGFR-2 is also involved in
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3the PI3K/p70 PI3K p70 S6K (S6 S6 kinase pathway by VEGFR-2 is also involved in VEGF-A-induced endothelial cell proliferation 107 (
12680VEGFAvascular endothelial growth factor AVEGF-A-induced5.8(S6 S6 kinase pathway by VEGFR-2 is also involved in VEGF-A-induced endothelial cell proliferation 107 ( Figure 2
18173ERAP1endoplasmic reticulum aminopeptidase 1PILSAP1.3PILSAP (puromycin-intensive puromycin-intensive leucyl-specific aminopeptidase plays a crucial role in the
8816PDPK13-phosphoinositide dependent protein kinase-1PDK11.6activation of this pathway via the binding and modification of PDK1 (phosphoinositide-dependent phosphoinositide-dependent kinase 1 108
12680VEGFAvascular endothelial growth factor AVEGF-induced5.8In addition recent studies have revealed various downstream mediators of VEGF-induced angiogenic signalling such as diacylglycerol kinase a 109 SRF (serum
11291SRFserum response factor (c-fos serum response element-binding transcription factor)SRF1.2of VEGF-induced angiogenic signalling such as diacylglycerol kinase a 109 SRF (serum serum response factor 110 SREBP (sterol-regulatory-element-binding sterol-regulatory-element-binding protein 111
6110IQGAP1IQ motif containing GTPase activating protein 1IQGAP10.6serum response factor 110 SREBP (sterol-regulatory-element-binding sterol-regulatory-element-binding protein 111 and IQGAP1 112
12680VEGFAvascular endothelial growth factor AVEGF-induced5.8using DNA microarrays have reported possible endogenous feedback inhibitors for VEGF-induced angiogenesis
3040RCAN1regulator of calcineurin 1DSCR11.6Vasohibin and DSCR1 (Down Down syndrome critical region protein 1 are significantly induced
12680VEGFAvascular endothelial growth factor AVEGF10.4Down syndrome critical region protein 1 are significantly induced by VEGF in endothelial cells 113 114
3040RCAN1regulator of calcineurin 1DSCR11.6Up-regulation of DSCR1 in endothelial cells inhibits the nuclear localization of NFAT (nuclear
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A is known to increase the vascular permeability of microvessels to
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A significantly accumulates in malignant ascites 116 and pleural effusion 117
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Consistent with a role in the regulation of vascular permeability VEGF-A induces endothelial fenestration in some vascular beds and in cultured
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A increases vascular permeability in mesenteric microvessels by activation of VEGFR-2
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3VEGF-A increases vascular permeability in mesenteric microvessels by activation of VEGFR-2 on endothelial cells and subsequent activation of PLC
9065PLCG1phospholipase C, gamma 1PLC0.9activation of VEGFR-2 on endothelial cells and subsequent activation of PLC
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3Other studies have also demonstrated the crucial role of VEGFR-2 signalling in the enhancement of vascular permeability however our recent
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6enhancement of vascular permeability is intensified by the activation of VEGFR-1 more than the proliferation of endothelial cells under some active
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3the proliferation of endothelial cells under some active signalling from VEGFR-2
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6This finding indicates the importance of VEGFR-1 signalling in vascular permeability
12680VEGFAvascular endothelial growth factor AVEGF-dependent5.8in specific Src family kinases has demonstrated no decrease in VEGF-dependent neovascularization but a complete ablation of vascular permeability in Src
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3blockade of Src prevents the disassociation of a complex comprising VEGFR-2 VE-cadherin and b -catenin with the same kinetics with which
12680VEGFAvascular endothelial growth factor AVEGF-mediated5.8b -catenin with the same kinetics with which it prevents VEGF-mediated vascular permeability and oedema 120
12680VEGFAvascular endothelial growth factor AVEGF-induced5.8activity of specific Src family kinases is essential for the VEGF-induced enhancement of vascular permeability through the disruption of the VEGFR-2/cadherin/catenin
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3enhancement of vascular permeability through the disruption of the VEGFR-2/cadherin/catenin VEGFR-2 cadherin catenin complex
1756CDH17cadherin 17, LI cadherin (liver-intestine)cadherin0.3of vascular permeability through the disruption of the VEGFR-2/cadherin/catenin VEGFR-2 cadherin catenin complex
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A can induce production of NO and endogenous NO can increase
7872NOS1nitric oxide synthase 1 (neuronal)NOS0.9Among the three isoforms of NOS (NO NO synthase eNOS (endothelial endothelial NOS plays a predominant
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS1.9Among the three isoforms of NOS (NO NO synthase eNOS (endothelial endothelial NOS plays a predominant role in VEGF-induced angiogenesis
7872NOS1nitric oxide synthase 1 (neuronal)NOS0.9three isoforms of NOS (NO NO synthase eNOS (endothelial endothelial NOS plays a predominant role in VEGF-induced angiogenesis and vascular permeability
12680VEGFAvascular endothelial growth factor AVEGF-induced5.8synthase eNOS (endothelial endothelial NOS plays a predominant role in VEGF-induced angiogenesis and vascular permeability 122
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS1.9Furthermore the activation of eNOS is regulated by the PI3K/Akt PI3K Akt pathway 123 124
8975PIK3CAphosphoinositide-3-kinase, catalytic, alpha polypeptidePI3K1.0Furthermore the activation of eNOS is regulated by the PI3K/Akt PI3K Akt pathway 123 124
391AKT1v-akt murine thymoma viral oncogene homolog 1Akt0.3the activation of eNOS is regulated by the PI3K/Akt PI3K Akt pathway 123 124
391AKT1v-akt murine thymoma viral oncogene homolog 1Rac1.1The small GTP-binding protein Rac which is also activated by PI3K has been implicated in
8975PIK3CAphosphoinositide-3-kinase, catalytic, alpha polypeptidePI3K1.0The small GTP-binding protein Rac which is also activated by PI3K has been implicated in the regulation of vascular permeability 125
6871MAPK1mitogen-activated protein kinase 1p382.2A recent study 126 has shown that inhibition of p38 MAPK activity abrogated VEGF-induced vascular permeability in vivo and in
6871MAPK1mitogen-activated protein kinase 1MAPK2.2A recent study 126 has shown that inhibition of p38 MAPK activity abrogated VEGF-induced vascular permeability in vivo and in vitro
12680VEGFAvascular endothelial growth factor AVEGF-induced5.8126 has shown that inhibition of p38 MAPK activity abrogated VEGF-induced vascular permeability in vivo and in vitro suggesting the involvement
6871MAPK1mitogen-activated protein kinase 1p382.2permeability in vivo and in vitro suggesting the involvement of p38 MAPK in the control of vascular permeability ( Figure 2
6871MAPK1mitogen-activated protein kinase 1MAPK2.2in vivo and in vitro suggesting the involvement of p38 MAPK in the control of vascular permeability ( Figure 2
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Numerous studies have established VEGF-A as a key angiogenic player in cancer
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A is expressed in most tumours and its expression correlates with
12680VEGFAvascular endothelial growth factor AVEGF-A7.6tumour cells tumour-associated stroma is also an important source of VEGF-A 127
12680VEGFAvascular endothelial growth factor AVEGF-A7.6The expression of VEGF-A mRNA is highest in hypoxic tumour cells adjacent to necrotic
12680VEGFAvascular endothelial growth factor AVEGF-A7.6adjacent to necrotic areas 16 indicating that the induction of VEGF-A by hypoxia in growing tumours can change the balance of
12680VEGFAvascular endothelial growth factor AVEGF10.4Consistent with this hypothesis capturing of VEGF or blocking of its signalling receptor VEGFR-2 by a VEGFR
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3hypothesis capturing of VEGF or blocking of its signalling receptor VEGFR-2 by a VEGFR tyrosine kinase inhibitor antisense oligonucleotides vaccination or
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR3.3VEGF or blocking of its signalling receptor VEGFR-2 by a VEGFR tyrosine kinase inhibitor antisense oligonucleotides vaccination or neutralizing antibodies reduced
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6Unlike in physiological angiogenesis VEGFR-1 signalling plays an important role in angiogenesis under pathological conditions
8893PGFplacental growth factorPlGF4.6Autiero et al 131 have proposed that PlGF regulates inter- and intra-molecular cross-talk between VEGFR-1 and VEGFR-2 amplifying
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6have proposed that PlGF regulates inter- and intra-molecular cross-talk between VEGFR-1 and VEGFR-2 amplifying VEGF-driven angiogenesis through VEGFR-2
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3that PlGF regulates inter- and intra-molecular cross-talk between VEGFR-1 and VEGFR-2 amplifying VEGF-driven angiogenesis through VEGFR-2
12680VEGFAvascular endothelial growth factor AVEGF-driven5.8regulates inter- and intra-molecular cross-talk between VEGFR-1 and VEGFR-2 amplifying VEGF-driven angiogenesis through VEGFR-2
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3intra-molecular cross-talk between VEGFR-1 and VEGFR-2 amplifying VEGF-driven angiogenesis through VEGFR-2
12680VEGFAvascular endothelial growth factor AVEGF10.4Several studies also describe the role of VEGF in carcinogenesis 132
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A and VEGFRs are constitutively expressed in the islet vasculature before
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFRs3.0VEGF-A and VEGFRs are constitutively expressed in the islet vasculature before and after
12680VEGFAvascular endothelial growth factor AVEGF-A7.6the initiation of angiogenesis (angiogenic angiogenic switch 133 however when VEGF-A is absent from islet b -cells of Rip1-Tag2 mice both
12680VEGFAvascular endothelial growth factor AVEGF-A7.6well as tumour growth are severely disrupted 134 indicating that VEGF-A plays a critical role in angiogenic switching and carcinogenesis
12680VEGFAvascular endothelial growth factor AVEGF-A7.6a component of the angiogenic switch as this proteinase makes VEGF-A available for the interaction with its receptors by releasing sequestered
12680VEGFAvascular endothelial growth factor AVEGF-A7.6available for the interaction with its receptors by releasing sequestered VEGF-A
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A impairs the endothelial barrier by disrupting a VE-cadherin/ VE-cadherin b
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A also induces the disruption of hepatocellular tight junctions which may
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3Pharmacological blockade of VEGFR-2 stabilizes the endothelial barrier function and suppresses tumour cell extravasation
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3tumour cell extravasation in vivo 136 suggesting the importance of VEGFR-2 signalling in this kind of tumour invasion and metastasis
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6Hiratsuka et al 138 have shown that VEGFR-1 signalling is also involved in tumour metastasis being linked to
7176MMP9matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)MMP-91.3involved in tumour metastasis being linked to the induction of MMP-9 in lung endothelial cells and to the facilitation of lung-specific
12680VEGFAvascular endothelial growth factor AVEGF10.4Besides bevacizumab many other VEGF inhibitors are being pursued clinically
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF acts as a pro-inflammatory cytokine by increasing the permeability of
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF is strongly expressed by epidermal keratinocytes in wound healing and
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Transgenic mice that overexpress VEGF-A specifically in the epidermis exhibit an increased density of tortuous
12680VEGFAvascular endothelial growth factor AVEGF-A7.6adhesion in postcapillary skin venules suggesting that enhanced expression of VEGF-A in epidermal keratinocytes is sufficient to develop psoriasis-like inflammatory skin
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Moreover heterozygous VEGF-A transgenic mice which do not spontaneously develop inflammatory skin lesions
8893PGFplacental growth factorPlGF-23.1Transgenic overexpression of PlGF-2 in epidermal keratinocytes also results in a significantly increased inflammatory
8893PGFplacental growth factorPlGF4.6in a significantly increased inflammatory response whereas a deficiency of PlGF results in a diminished and abbreviated inflammatory response 145 suggesting
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6diminished and abbreviated inflammatory response 145 suggesting the importance of VEGFR-1 signalling in chronic skin inflammation
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Local production of VEGF-A in arthritic synovial tissue has been documented 16 and appears
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Subsequently VEGF-A has been shown to be important in the pathogenesis of
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6by suppressing synovial inflammation and neovascularization emphasizing the importance of VEGFR-1 signalling in the destruction
12681VEGFBvascular endothelial growth factor BVEGF-B1.8The reduction of synovial inflammation in VEGF-B mice 47 also implies a critical role for VEGFR-1 signalling
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6in VEGF-B mice 47 also implies a critical role for VEGFR-1 signalling in RA
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Exaggerated levels of VEGF-A have been detected in tissues and biological samples from people
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF has been postulated to contribute to asthmatic tissue oedema through
12680VEGFAvascular endothelial growth factor AVEGF10.4A recent study using lung-targeted VEGF 165 transgenic mice has revealed a novel function of VEGF-A
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF 165 transgenic mice has revealed a novel function of VEGF-A in allergic responses
12680VEGFAvascular endothelial growth factor AVEGF-A7.6In these mice VEGF-A induces asthma-like inflammation airway and vascular remodelling and airway hyper-responsiveness
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A also enhances respiratory sensitization to antigen as well as T
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Thus VEGF-A has a critical role in pulmonary T H 2 inflammation
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Other studies have provided evidence for a role for VEGF-A as a pro-inflammatory mediator in allograft rejection 152 and neointimal
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A mRNA expression not normally found in the adult mouse brain
12680VEGFAvascular endothelial growth factor AVEGF-A7.6adult mouse brain is up-regulated after cerebral ischaemia and elevated VEGF-A levels can be detected as early as 3 h after
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Previous studies have demonstrated that the antagonism of VEGF-A results in reduced oedema and tissue damage after ischaemia implicating
12680VEGFAvascular endothelial growth factor AVEGF-A7.6results in reduced oedema and tissue damage after ischaemia implicating VEGF-A in the pathophysiology of stroke 155
12680VEGFAvascular endothelial growth factor AVEGF-A-induced5.8al 156 have reported that Src mice are resistant to VEGF-A-induced vascular permeability and show decreased infarct volumes after stroke
12680VEGFAvascular endothelial growth factor AVEGF-A7.6permeability protecting wild-type mice from ischaemia-induced brain damage without influencing VEGF-A expression
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Sun et al 157 have reported that intracerebroventricular administration of VEGF-A reduces infarct size improves neurological performance and enhances the delayed
12680VEGFAvascular endothelial growth factor AVEGF-A7.6These conflicting results appear to reflect dual roles of VEGF-A in stroke neuroprotective and pro-inflammatory effects
12680VEGFAvascular endothelial growth factor AVEGF-A7.6through the internal carotid artery low and intermediate doses of VEGF-A significantly promote neuroprotection of the ischaemic brain whereas a high
12680VEGFAvascular endothelial growth factor AVEGF-A7.6neuroprotection of the ischaemic brain whereas a high dose of VEGF-A offers no neuroprotection to the ischaemic brain or the damaged
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Further studies are required for the therapeutic application of VEGF-A against stroke
12680VEGFAvascular endothelial growth factor AVEGF10.4Extensive evidence has suggested a causal role of VEGF in several diseases of the human eye in which neovascularization
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF levels are increased in the vitreous and retina of patients
12680VEGFAvascular endothelial growth factor AVEGF10.4Subsequent studies using various VEGF inhibitors have confirmed that VEGF plays a central role in
12680VEGFAvascular endothelial growth factor AVEGF10.4Subsequent studies using various VEGF inhibitors have confirmed that VEGF plays a central role in ischaemia-induced intraocular neovascularization 159
12680VEGFAvascular endothelial growth factor AVEGF10.4161 have reported that deletion of the HRE in the VEGF promoter reduces hypoxic VEGF expression in the spinal cord and
12680VEGFAvascular endothelial growth factor AVEGF10.4deletion of the HRE in the VEGF promoter reduces hypoxic VEGF expression in the spinal cord and causes adult-onset progressive motor
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF 165 promotes survival of motor neurons during hypoxia through binding
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3165 promotes survival of motor neurons during hypoxia through binding VEGFR-2 and NRP-1 161
8004NRP1neuropilin 1NRP-10.8survival of motor neurons during hypoxia through binding VEGFR-2 and NRP-1 161
12680VEGFAvascular endothelial growth factor AVEGF-A7.6A subsequent study has revealed that VEGF-A is a modifier associated with motor neuron degeneration in human
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A treatment increases the life expectancy of ALS mice without causing
12680VEGFAvascular endothelial growth factor AVEGF-A7.6mice without causing toxic side effects 163 164 indicating that VEGF-A has neuroprotective effects on motor neurons and treatment with VEGF-A
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A has neuroprotective effects on motor neurons and treatment with VEGF-A could be one of the most effective therapies for ALS
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6al 165 recently provided evidence for a novel function of VEGFR-1 in LSECs (liver liver sinusoidal endothelial cells
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6The activation of VEGFR-1 results in the paracrine release of HGF (hepatocyte hepatocyte growth
6018IL6interleukin 6 (interferon, beta 2)HGF1.8The activation of VEGFR-1 results in the paracrine release of HGF (hepatocyte hepatocyte growth factor IL-6 (interleukin-6) interleukin-6 and other hepatotrophic
6018IL6interleukin 6 (interferon, beta 2)IL-61.8in the paracrine release of HGF (hepatocyte hepatocyte growth factor IL-6 (interleukin-6) interleukin-6 and other hepatotrophic molecules by LSECs to the
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A has no direct mitogenic effect on hepatocytes
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6A VEGFR-1 agonist protected the liver from CCl 4 -induced damage in
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF was originally described as a specific angiogenic and permeability-inducing factor
12680VEGFAvascular endothelial growth factor AVEGF10.4emerging evidence has revealed that the role of the VEGF/VEGFR VEGF VEGFR system extends far beyond previous expectations
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR3.3evidence has revealed that the role of the VEGF/VEGFR VEGF VEGFR system extends far beyond previous expectations
12680VEGFAvascular endothelial growth factor AVEGF10.4First a wide variety of VEGF family proteins and numerous splicing variants have been identified and
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF family proteins have been utilized even in snake venoms and
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFRs3.0Secondly several different VEGFRs have been shown to be essential but the interaction between
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6VEGFR-1 has a negative regulatory role in embryonic angiogenesis but functions
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3signal transducer in some cases individually and sometimes synergistically with VEGFR-2 via the intra- and inter-molecular cross-talk between these two receptors
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3An association between VEGFR-2 and VEGFR-3 has also been reported 166
3767FLT4fms-related tyrosine kinase 4VEGFR-30.6An association between VEGFR-2 and VEGFR-3 has also been reported 166
12680VEGFAvascular endothelial growth factor AVEGF10.4Thirdly it has been shown that the VEGF/VEGFR VEGF VEGFR system has multiple functions such as the induction of
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR3.3Thirdly it has been shown that the VEGF/VEGFR VEGF VEGFR system has multiple functions such as the induction of tumour
12680VEGFAvascular endothelial growth factor AVEGF10.4VEGF is also important for memory and learning 167
12680VEGFAvascular endothelial growth factor AVEGF10.4other molecules have been found to associate with the VEGF/VEGFR VEGF VEGFR system
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR3.3molecules have been found to associate with the VEGF/VEGFR VEGF VEGFR system
12680VEGFAvascular endothelial growth factor AVEGF10.4are required to achieve a comprehensive understanding of the VEGF/VEGFR VEGF VEGFR system however the recent progress in the molecular and
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR3.3required to achieve a comprehensive understanding of the VEGF/VEGFR VEGF VEGFR system however the recent progress in the molecular and biological
12680VEGFAvascular endothelial growth factor AVEGF10.4angiogenesis inflammation signal transduction tumour vascular endothelial growth factor (VEGF), VEGF vascular permeability
3040RCAN1regulator of calcineurin 1DSCR11.6Abbreviations ALS amyotrophic lateral sclerosis DSCR1 Down syndrome critical region protein 1 ECM extracellular matrix ERK
6871MAPK1mitogen-activated protein kinase 1ERK2.2DSCR1 Down syndrome critical region protein 1 ECM extracellular matrix ERK extracellular signal-regulated kinase FAK focal adhesion kinase HIF-1 hypoxia-inducible factor-1
9611PTK2PTK2 protein tyrosine kinase 2FAK0.3region protein 1 ECM extracellular matrix ERK extracellular signal-regulated kinase FAK focal adhesion kinase HIF-1 hypoxia-inducible factor-1 HRE hypoxia response element
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)HIF-10.6extracellular matrix ERK extracellular signal-regulated kinase FAK focal adhesion kinase HIF-1 hypoxia-inducible factor-1 HRE hypoxia response element HUVEC human umbilical vein
6871MAPK1mitogen-activated protein kinase 1MAPK2.2endothelial cell LSEC liver sinusoidal endothelial cell mAb monoclonal antibody MAPK mitogen-activated protein kinase MMP matrix metalloproteinase NFATc nuclear factor of
7775NFATC1nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1NFATc2.5mAb monoclonal antibody MAPK mitogen-activated protein kinase MMP matrix metalloproteinase NFATc nuclear factor of activated T-cell NO nitric oxide NOS NO
7872NOS1nitric oxide synthase 1 (neuronal)NOS0.9metalloproteinase NFATc nuclear factor of activated T-cell NO nitric oxide NOS NO synthase eNOS endothelial NOS NRP neuropilin PAIP2 polyadenylated-binding protein-interacting
7876NOS3nitric oxide synthase 3 (endothelial cell)eNOS1.9factor of activated T-cell NO nitric oxide NOS NO synthase eNOS endothelial NOS NRP neuropilin PAIP2 polyadenylated-binding protein-interacting protein 2 PDK1
7872NOS1nitric oxide synthase 1 (neuronal)NOS0.9activated T-cell NO nitric oxide NOS NO synthase eNOS endothelial NOS NRP neuropilin PAIP2 polyadenylated-binding protein-interacting protein 2 PDK1 phosphoinositide-dependent kinase
8004NRP1neuropilin 1NRP0.8T-cell NO nitric oxide NOS NO synthase eNOS endothelial NOS NRP neuropilin PAIP2 polyadenylated-binding protein-interacting protein 2 PDK1 phosphoinositide-dependent kinase 1
17970PAIP2poly(A) binding protein interacting protein 2PAIP20.6nitric oxide NOS NO synthase eNOS endothelial NOS NRP neuropilin PAIP2 polyadenylated-binding protein-interacting protein 2 PDK1 phosphoinositide-dependent kinase 1 PI3K phosphoinositide
8816PDPK13-phosphoinositide dependent protein kinase-1PDK11.6eNOS endothelial NOS NRP neuropilin PAIP2 polyadenylated-binding protein-interacting protein 2 PDK1 phosphoinositide-dependent kinase 1 PI3K phosphoinositide 3-kinase PILSAP puromycin-intensive leucyl-specific aminopeptidase
8975PIK3CAphosphoinositide-3-kinase, catalytic, alpha polypeptidePI3K1.0neuropilin PAIP2 polyadenylated-binding protein-interacting protein 2 PDK1 phosphoinositide-dependent kinase 1 PI3K phosphoinositide 3-kinase PILSAP puromycin-intensive leucyl-specific aminopeptidase PKC protein kinase C
18173ERAP1endoplasmic reticulum aminopeptidase 1PILSAP1.3protein-interacting protein 2 PDK1 phosphoinositide-dependent kinase 1 PI3K phosphoinositide 3-kinase PILSAP puromycin-intensive leucyl-specific aminopeptidase PKC protein kinase C PLC phospholipase C
9065PLCG1phospholipase C, gamma 1PLC0.9phosphoinositide 3-kinase PILSAP puromycin-intensive leucyl-specific aminopeptidase PKC protein kinase C PLC phospholipase C PlGF placenta growth factor pVHL von Hippel-Lindau tumour
8893PGFplacental growth factorPlGF4.6puromycin-intensive leucyl-specific aminopeptidase PKC protein kinase C PLC phospholipase C PlGF placenta growth factor pVHL von Hippel-Lindau tumour suppressor protein RA
10436RPS6KB1ribosomal protein S6 kinase, 70kDa, polypeptide 1S6K1.0tumour suppressor protein RA rheumatoid arthritis RTK receptor tyrosine kinase S6K S6 kinase Tag T antigen T H 2 T-helper type
12680VEGFAvascular endothelial growth factor AVEGF10.4antigen T H 2 T-helper type 2 UTR untranslated region VEGF vascular endothelial growth factor VEGFR VEGF receptor sVEGFR-1 soluble VEGFR-1
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR3.3type 2 UTR untranslated region VEGF vascular endothelial growth factor VEGFR VEGF receptor sVEGFR-1 soluble VEGFR-1 svVEGF snake venom VEGF Tf
12680VEGFAvascular endothelial growth factor AVEGF10.42 UTR untranslated region VEGF vascular endothelial growth factor VEGFR VEGF receptor sVEGFR-1 soluble VEGFR-1 svVEGF snake venom VEGF Tf svVEGF
3763FLT1fms-related tyrosine kinase 1 (vascular endothelial growth factor/vascular permeability factor receptor)VEGFR-10.6VEGF vascular endothelial growth factor VEGFR VEGF receptor sVEGFR-1 soluble VEGFR-1 svVEGF snake venom VEGF Tf svVEGF Trimeresurus flavoviridis svVEGF VPF
12680VEGFAvascular endothelial growth factor AVEGF10.4factor VEGFR VEGF receptor sVEGFR-1 soluble VEGFR-1 svVEGF snake venom VEGF Tf svVEGF Trimeresurus flavoviridis svVEGF VPF vascular permeability factor
12680VEGFAvascular endothelial growth factor AVPF5.8VEGFR-1 svVEGF snake venom VEGF Tf svVEGF Trimeresurus flavoviridis svVEGF VPF vascular permeability factor
12680VEGFAvascular endothelial growth factor AVEGF10.4The VEGF (vascular vascular endothelial growth factor family and its receptors are
12680VEGFAvascular endothelial growth factor AVEGF10.4Currently the VEGF family consists of VEGF-A PlGF (placenta placenta growth factor VEGF-B
12680VEGFAvascular endothelial growth factor AVEGF-A7.6Currently the VEGF family consists of VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and
8893PGFplacental growth factorPlGF4.6Currently the VEGF family consists of VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and snake
12681VEGFBvascular endothelial growth factor BVEGF-B1.8VEGF family consists of VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and snake venom VEGF
12682VEGFCvascular endothelial growth factor CVEGF-C1.8family consists of VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and snake venom VEGF
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)VEGF-D1.3consists of VEGF-A PlGF (placenta placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and snake venom VEGF
12680VEGFAvascular endothelial growth factor AVEGF10.4placenta growth factor VEGF-B VEGF-C VEGF-D VEGF-E and snake venom VEGF
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A has at least nine subtypes due to the alternative splicing
12680VEGFAvascular endothelial growth factor AVEGF10.4Although the VEGF 165 isoform plays a central role in vascular development recent
12680VEGFAvascular endothelial growth factor AVEGF10.4role in vascular development recent studies have demonstrated that each VEGF isoform plays distinct roles in vascular patterning and arterial development
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A binds to and activates two tyrosine kinase receptors VEGFR (VEGF
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR3.3VEGF-A binds to and activates two tyrosine kinase receptors VEGFR (VEGF VEGF receptor -1 and VEGFR-2
12680VEGFAvascular endothelial growth factor AVEGF10.4binds to and activates two tyrosine kinase receptors VEGFR (VEGF VEGF receptor -1 and VEGFR-2
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3two tyrosine kinase receptors VEGFR (VEGF VEGF receptor -1 and VEGFR-2
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR-24.3VEGFR-2 mediates most of the endothelial growth and survival signals but
12680VEGFAvascular endothelial growth factor AVEGF-A7.6In solid tumours VEGF-A and its receptor are involved in carcinogenesis invasion and distant
12680VEGFAvascular endothelial growth factor AVEGF-A7.6VEGF-A also has a neuroprotective effect on hypoxic motor neurons and
12680VEGFAvascular endothelial growth factor AVEGF10.4progress in the molecular and biological understanding of the VEGF/VEGFR VEGF VEGFR system provides us with novel and promising therapeutic strategies
6307KDRkinase insert domain receptor (a type III receptor tyrosine kinase)VEGFR3.3in the molecular and biological understanding of the VEGF/VEGFR VEGF VEGFR system provides us with novel and promising therapeutic strategies and
12680VEGFAvascular endothelial growth factor Avascular endothelial growth factor1.0foremost among these is the vegf vascular endothelial growth factor family and vegfrs vegf receptors .
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a also referred to as vpf vascular permeability factor an important regulator of endothelial cell physiology was identified approx. 15 years ago [ 1 2 ] and has been recognized as the major growth fact
12680VEGFAvascular endothelial growth factor Avascular permeability factor1.0vegf a also referred to as vpf vascular permeability factor an important regulator of endothelial cell physiology was identified approx. 15 years ago [ 1 2 ] and has been recognized as the major growth factor that is relatively specific for endothelial cells.
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a is a dimeric glycoprotein essential for many angiogenic processes in normal and abnormal states such as tumour vascularization mainly by interacting with two tyrosine kinase receptors vegfr 1 [also k
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a exhibits two major biological activities: one is the capacity to stimulate vascular endothelial cell proliferation [ 1 6 7 ] and the other is the ability to increase vascular permeability [ 2 8 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a also promotes the survival and migration of endothelial cells.
12680VEGFAvascular endothelial growth factor Avegf a1.0currently the vegf family includes vegf a plgf placenta growth factor vegf b vegf c vegf d vegf e and svvegf snake venom vegf .
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)vegf d1.0currently the vegf family includes vegf a plgf placenta growth factor vegf b vegf c vegf d vegf e and svvegf snake venom vegf .
8893PGFplacental growth factorplacenta growth factor1.0currently the vegf family includes vegf a plgf placenta growth factor vegf b vegf c vegf d vegf e and svvegf snake venom vegf .
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a
8800PDGFBplatelet-derived growth factor beta polypeptide (simian sarcoma viral (v-sis) oncogene homolog)platelet derived growth factor1.0structurally vegf belongs to the vegf/pdgf platelet derived growth factor supergene family.
12680VEGFAvascular endothelial growth factor Avegf a1.0the human vegf a gene is organized into eight exons separated by seven introns [ 10 11 ] and is located at 6p21.3 [ 12 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0human vegf a has at least nine subtypes due to the alternative splicing of a single gene: vegf 121 vegf 145 vegf 148 vegf 162 vegf 165 vegf 165 b vegf 183 vegf 189 and vegf 206 [ 13 14 ] figure 1 .
8004NRP1neuropilin 1neuropilin 11.0vegf 165 binds the coreceptors nrp 1 neuropilin 1 [ 20 ] and nrp 2 neuropilin 2 whereas vegf 145 binds only nrp 2 [ 21 ] figure 2 .
8005NRP2neuropilin 2neuropilin 21.0vegf 165 binds the coreceptors nrp 1 neuropilin 1 [ 20 ] and nrp 2 neuropilin 2 whereas vegf 145 binds only nrp 2 [ 21 ] figure 2 .
12372TSHBthyroid stimulating hormone, betathyroid stimulating hormone1.0gene expression of vegf is regulated by a variety of stimuli such as hypoxia growth factors transformation p53 mutation oestrogen tsh thyroid stimulating hormone tumour promoters and no nitric oxide .
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)hypoxia inducible factor 11.0it is now well established that hif 1 hypoxia inducible factor 1 is a key mediator of hypoxic responses.
18420SETD2SET domain containing 2hif 11.0it is now well established that hif 1 hypoxia inducible factor 1 is a key mediator of hypoxic responses.
18420SETD2SET domain containing 2hif 11.0hif 1 is a transcriptional activator composed of hif 1 a and hif 1 b subunits.
18420SETD2SET domain containing 2hif 11.0both hif 1 a and hif 1 b are constitutively expressed in various types of tumour.
18420SETD2SET domain containing 2hif 11.0under normal oxygenation conditions hif 1 a is scarcely detectable because it is targeted for rapid destruction by an e3 ubiquitin ligase containing pvhl von hippel lindau tumour suppressor protein .
8607PARK2Parkinson disease (autosomal recessive, juvenile) 2, parkine3 ubiquitin ligase1.0under normal oxygenation conditions hif 1 a is scarcely detectable because it is targeted for rapid destruction by an e3 ubiquitin ligase containing pvhl von hippel lindau tumour suppressor protein .
18420SETD2SET domain containing 2hif 11.0the interaction between pvhl and a specific domain of the hif 1 a subunit is regulated through hydroxylation of a proline residue pro in hif 1 a by prolyl 4 hydroxylase which requires molecular oxygen and iron for its activity.
8546P4HA1procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha polypeptide Iprolyl 4 hydroxylase1.0the interaction between pvhl and a specific domain of the hif 1 a subunit is regulated through hydroxylation of a proline residue pro in hif 1 a by prolyl 4 hydroxylase which requires molecular oxygen and iron for its activity.
18420SETD2SET domain containing 2hif 11.0under hypoxic conditions hif 1 a expression increases as a result of suppressed prolyl hydroxylation of hif 1 a and decreased ubiquitination and degradation [ 26 27 ].
18420SETD2SET domain containing 2hif 11.0furthermore hypoxia inhibits the oxygen dependent hydroxylation of an asparagine residue asn in hif 1 a in the c terminal transactivation domain of hif 1 a to promote interaction with the p300/cbp [creb camp response element binding protein binding protein] co activator and induce a hre hypoxia response element driven transcription of the vegf gene [
3796FOSv-fos FBJ murine osteosarcoma viral oncogene homologap 11.0very recently gerald et al. [ 29 ] have demonstrated that jund a member of the ap 1 family of transcription factors is involved in the regulation of prolyl hydroxylase activity.
12680VEGFAvascular endothelial growth factor Avegf a1.0consequently hif 1 a protein accumulates under normoxic conditions and the transcription of vegf a is increased [ 29 ].
18420SETD2SET domain containing 2hif 11.0consequently hif 1 a protein accumulates under normoxic conditions and the transcription of vegf a is increased [ 29 ].
8893PGFplacental growth factorplgf 21.0alternative splicing of the human plgf gene generates four isoforms which differ in size and binding properties: plgf 1 plgf 131 plgf 2 plgf 152 plgf 3 plgf 203 and plgf 4 plgf 224 [ 37 39 ] figure 1 .
913AZU1azurocidin 1 (cationic antimicrobial protein 37)heparin binding protein1.0plgf 1 is the shortest isoform and a non heparin binding protein.
8893PGFplacental growth factorplgf 21.0plgf 2 is able to bind heparin and the co receptors nrp 1 and nrp 2 due to the insertion of a highly basic 21 amino acid sequence encoded by exon vi near the c terminus [ 37 ] figure 2 .
8893PGFplacental growth factorplgf 21.0plgf 4 consists of the same sequence of plgf 3 plus a heparin binding domain previously thought to be present only in plgf 2 [ 39 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0the crystal structure of human plgf 1 has shown that this protein is structurally similar to vegf a [ 40 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0furthermore despite this moderate sequence conservation plgf and vegf a bind to the same binding interface of vegfr 1 in a very similar fashion [ 41 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0however recent studies have reported that unlike in vegf a n glycosylation in plgf plays an important role in vegfr 1 binding [ 42 ].
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)vegf d1.0vegf c and vegf d
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)vegf d1.0vegf c contains a region sharing approx. 30% amino acid identity with vegf 165 ; however it is more closely related to vegf d by virtue of the presence of n and c terminal extensions that are not found in other vegf family members [ 49 ] figure 1 .
12680VEGFAvascular endothelial growth factor Avegf a1.0both vegf c and vegf d bind and activate vegfr 3 flt 4; a member of the vegfr family that does not bind vegf a as well as vegfr 2 and are mitogenic for cultured endothelial cells.
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)vegf d1.0both vegf c and vegf d bind and activate vegfr 3 flt 4; a member of the vegfr family that does not bind vegf a as well as vegfr 2 and are mitogenic for cultured endothelial cells.
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)vegf d1.0both vegf c and vegf d are produced as a preproprotein with long n and c terminal propeptides flanking the vegf homology domain.
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)vegf d1.0this activation of vegf c and vegf d by proteolytic cleavage is at least partly regulated by the serine protease plasmin [ 50 ].
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)vegf d1.0in vitro vegf c and vegf d stimulate the migration and mitogenesis of cultured endothelial cells [ 49 ].
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)vegf d1.0less is known of the function of vegf d but stacker et al. [ 53 ] have revealed that vegf d induces the formation of lymphatics within tumours and promotes the metastasis of tumour cells.
12680VEGFAvascular endothelial growth factor Avegf a1.0homologues of vegf have also been identified in the genome of the parapoxvirus orf virus [ 54 ] and have been shown to have vegf a like activities.
12680VEGFAvascular endothelial growth factor Avegf a1.0takahashi et al. [ 61 ] have shown that snakes utilize these venom specific vegfs in addition to vegf a. svvegfs function as dimers and each chain comprises approx. 110 122 amino acid residues.
12680VEGFAvascular endothelial growth factor Avegf a1.0vegfr 1 is a 180 kda high affinity receptor for vegf a vegf b plgf and tf svvegf.
12680VEGFAvascular endothelial growth factor Avegf a1.0the second ig domain of vegfr 1 is the major binding site for vegf a and plgf [ 16 41 67 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0vegfr 1 binds vegf a with at least 10 fold higher affinity than vegfr 2 k d =10 30 pm [ 16 ]; however ligand binding results in a maximal 2 fold increase in kinase activity.
12680VEGFAvascular endothelial growth factor Avegf a1.0vegfr 1 blocking antibodies prevent the migration but not proliferation of huvecs human umbilical vein endothelial cells in response to vegf a indicating the involvement of vegfr 1 in endothelial cell migration [ 68 ].
9718PXNpaxillinpaxillin1.0ulate the reorganization of actin via p38 mapk mitogen activated protein kinase whereas vegfr 2 contributes to the re organization of the cytoskeleton by phosphorylating fak focal adhesion kinase and paxillin figure 2 suggesting a different contribution of the two receptors to the chemotactic response.
12680VEGFAvascular endothelial growth factor Avegf a1.0iced form of vegfr 1 that encodes a soluble truncated form of the receptor containing only the first six ig domains has been cloned from a huvec cdna library [ 16 ]. svegfr 1 soluble vegfr 1 inhibits vegf a activity by sequestering vegf a from signalling receptors and by forming non signalling heterodimers with vegfr 2 [ 69 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0 activity by sequestering vegf a from signalling receptors and by forming non signalling heterodimers with vegfr 2 [ 69 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0vegfr 2 is a 200 230 kda high affinity receptor for vegf a k d =75 760 pm vegf e and svvegfs as well as the processed form of vegf c and vegf d.
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)vegf d1.0vegfr 2 is a 200 230 kda high affinity receptor for vegf a k d =75 760 pm vegf e and svvegfs as well as the processed form of vegf c and vegf d.
12680VEGFAvascular endothelial growth factor Avegf a1.0the binding site for vegf a has been mapped to the second and third ig domains [ 74 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0tyrosine phosphorylation sites in human vegfr 2 bound to vegf a are tyr and tyr in the kinase insert domain tyr and tyr in the kinase domain and tyr and tyr in the c terminal tail.
12680VEGFAvascular endothelial growth factor Avegf a1.0among them tyr and tyr are the two major vegf a dependent autophosphorylation sites [ 76 ].
15917PLCB1phospholipase C, beta 1 (phosphoinositide-specific)phospholipase c1.0tyr creates a binding site for the vegfr associated protein [ 77 ] and tyr creates a binding site for sck [ 78 ] shb [ 79 ] and plc phospholipase c g [ 76 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0vegfr 2 is the major mediator of the mitogenic angiogenic and permeability enhancing effects of vegf a.
12680VEGFAvascular endothelial growth factor Avegf a1.0byzova et al. [ 84 ] have reported that the activation of vegfr 2 by vegf a results in the pi3k/akt dependent activation of several integrins leading to enhanced cell adhesion and migration.
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)vegf d1.0vegfr 3 is a 195 kda high affinity receptor for vegf c and vegf d.
9393PRKCAprotein kinase C, alphaprotein kinase c1.0the phosphorylation of vegfr 3 has been shown to lead to a pi3k dependent activation of akt and pkc protein kinase c dependent activation of p42/p44 mapk [ 88 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0nrp 1 is a 130 140 kda cell surface glycoprotein first identified as a semaphorin receptor involved in neuronal guidance [ 90 ] and subsequently found as an isoform specific receptor for vegf a [ 20 ].
9103PLXNB1plexin B1semaphorin receptor1.0nrp 1 is a 130 140 kda cell surface glycoprotein first identified as a semaphorin receptor involved in neuronal guidance [ 90 ] and subsequently found as an isoform specific receptor for vegf a [ 20 ].
4281GJA8gap junction protein, alpha 8, 50kDacell surface glycoprotein1.0nrp 1 is a 130 140 kda cell surface glycoprotein first identified as a semaphorin receptor involved in neuronal guidance [ 90 ] and subsequently found as an isoform specific receptor for vegf a [ 20 ].
8893PGFplacental growth factorplgf 21.0nrp 1 is able to bind vegf 165 vegf b plgf 2 and some vegf e variants whereas nrp 2 can bind vegf 145 vegf 165 plgf 2 and vegf c.
9106PLXNC1plexin C1plexin1.0it has been shown that both nrps can join with receptors belonging to the plexin family and such plexin/nrp complexes are able to transduce signals as the physiological receptor of class 3 semaphorins [ 91 92 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0in addition a 2 to 3 fold overexpression of vegf a from its endogenous locus results in severe abnormalities in heart development and lethality at embryonic days 12.5 and 14 [ 100 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0these results demonstrate the importance of tightly regulating vegf a expression during embryonic development.
12680VEGFAvascular endothelial growth factor Avegf a1.0takahashi et al. [ 76 ] have shown that tyr and tyr are two major vegf a dependent autophosphorylation sites in vegfr 2.
6879MAPK6mitogen-activated protein kinase 6extracellular signal regulated kinase1.0however only autophosphorylation of tyr is crucial for vegf dependent endothelial cell proliferation via the plc g /pkc/raf/mek [mapk/erk extracellular signal regulated kinase kinase]/erk pathway.
12680VEGFAvascular endothelial growth factor Avegf a1.0sphorylation of tyr appears to be required to trigger the sequential activation of cdc42 and p38 mapk and to drive p38 mapk mediated actin remodelling in stress fibres in endothelial cells exposed to vegf a [ 106 ].
10436RPS6KB1ribosomal protein S6 kinase, 70kDa, polypeptide 1p70 s6k1.0the activation of the pi3k/p70 s6k s6 kinase pathway by vegfr 2 is also involved in vegf a induced endothelial cell proliferation [ 107 ] figure 2 .
12680VEGFAvascular endothelial growth factor Avegf a1.0the activation of the pi3k/p70 s6k s6 kinase pathway by vegfr 2 is also involved in vegf a induced endothelial cell proliferation [ 107 ] figure 2 .
13164CNBPCCHC-type zinc finger, nucleic acid binding proteinsterol regulatory element binding protein1.0in addition recent studies have revealed various downstream mediators of vegf induced angiogenic signalling such as diacylglycerol kinase a [ 109 ] srf serum response factor [ 110 ] srebp sterol regulatory element binding protein [ 111 ] and iqgap1 [ 112 ].
11291SRFserum response factor (c-fos serum response element-binding transcription factor)serum response factor1.0in addition recent studies have revealed various downstream mediators of vegf induced angiogenic signalling such as diacylglycerol kinase a [ 109 ] srf serum response factor [ 110 ] srebp sterol regulatory element binding protein [ 111 ] and iqgap1 [ 112 ].
2856DGKQdiacylglycerol kinase, theta 110kDadiacylglycerol kinase1.0in addition recent studies have revealed various downstream mediators of vegf induced angiogenic signalling such as diacylglycerol kinase a [ 109 ] srf serum response factor [ 110 ] srebp sterol regulatory element binding protein [ 111 ] and iqgap1 [ 112 ].
19964VASH1vasohibin 1vasohibin1.0vasohibin and dscr1 down syndrome critical region protein 1 are significantly induced by vegf in endothelial cells [ 113 114 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a is known to increase the vascular permeability of microvessels to circulating macromolecules [ 14 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a significantly accumulates in malignant ascites [ 116 ] and pleural effusion [ 117 ] suggesting that it plays a fundamental role in the accumulation of malignant fluid through the enhancement of vascu
12680VEGFAvascular endothelial growth factor Avegf a1.0consistent with a role in the regulation of vascular permeability vegf a induces endothelial fenestration in some vascular beds and in cultured adrenal endothelial cells the extravasation of ferritin by way of the vvo vesiculo vacuolar organelle [ 14 ] and disorganization
1764CDH5cadherin 5, type 2, VE-cadherin (vascular epithelium)ve cadherin1.0scular beds and in cultured adrenal endothelial cells the extravasation of ferritin by way of the vvo vesiculo vacuolar organelle [ 14 ] and disorganization of endothelial junctional proteins such as ve cadherin and occludin [ 118 ].
8104OCLNoccludinoccludin1.0in cultured adrenal endothelial cells the extravasation of ferritin by way of the vvo vesiculo vacuolar organelle [ 14 ] and disorganization of endothelial junctional proteins such as ve cadherin and occludin [ 118 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a increases vascular permeability in mesenteric microvessels by activation of vegfr 2 on endothelial cells and subsequent activation of plc.
1764CDH5cadherin 5, type 2, VE-cadherin (vascular epithelium)ve cadherin1.0in addition blockade of src prevents the disassociation of a complex comprising vegfr 2 ve cadherin and b catenin with the same kinetics with which it prevents vegf mediated vascular permeability and oedema [ 120 ].
6207JUPjunction plakoglobincatenin1.0in addition blockade of src prevents the disassociation of a complex comprising vegfr 2 ve cadherin and b catenin with the same kinetics with which it prevents vegf mediated vascular permeability and oedema [ 120 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a can induce production of no and endogenous no can increase vascular permeability [ 121 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0numerous studies have established vegf a as a key angiogenic player in cancer.
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a is expressed in most tumours and its expression correlates with tumour progression.
12680VEGFAvascular endothelial growth factor Avegf a1.0in addition to tumour cells tumour associated stroma is also an important source of vegf a [ 127 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0the expression of vegf a mrna is highest in hypoxic tumour cells adjacent to necrotic areas [ 16 ] indicating that the induction of vegf a by hypoxia in growing tumours can change the balance of inhibitors and activators of angiogenesis leading to the growth of new blood vessels into tumour.
5176KRR1KRR1, small subunit (SSU) processome component, homolog (yeast)rip11.0rip1 tag2 t antigen 2 mice develop islet tumours of the pancreas by 12 14 weeks of age as a result of expression of the sv40 tag oncogene in insulin producing b cells.
6081INSinsulininsulin1.0rip1 tag2 t antigen 2 mice develop islet tumours of the pancreas by 12 14 weeks of age as a result of expression of the sv40 tag oncogene in insulin producing b cells.
5176KRR1KRR1, small subunit (SSU) processome component, homolog (yeast)rip11.0vegf a and vegfrs are constitutively expressed in the islet vasculature before and after the initiation of angiogenesis angiogenic switch [ 133 ]; however when vegf a is absent from islet b cells of rip1 tag2 mice both angiogenic switching and carcinogenesis as well as tumour growth are severely disrupted [ 134 ] indicating that vegf a plays a critical role in angiogenic switching and carcinogenesis.
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a and vegfrs are constitutively expressed in the islet vasculature before and after the initiation of angiogenesis angiogenic switch [ 133 ]; however when vegf a is absent from islet b cells of rip1 tag2 mice both angiogenic switching and carcinogenesis as well as tumour growth are severely disrupted [ 134 ] indicating that vegf a plays a critical role in ang
12680VEGFAvascular endothelial growth factor Avegf a1.0 is absent from islet b cells of rip1 tag2 mice both angiogenic switching and carcinogenesis as well as tumour growth are severely disrupted [ 134 ] indicating that vegf a plays a critical role in angiogenic switching and carcinogenesis.
12680VEGFAvascular endothelial growth factor Avegf a1.0bergers et al. [ 135 ] have revealed that mmp matrix metalloproteinase 9 is also a component of the angiogenic switch as this proteinase makes vegf a available for the interaction with its receptors by releasing sequestered vegf a.
12680VEGFAvascular endothelial growth factor Avegf a1.0 available for the interaction with its receptors by releasing sequestered vegf a.
7176MMP9matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)matrix metalloproteinase 91.0bergers et al. [ 135 ] have revealed that mmp matrix metalloproteinase 9 is also a component of the angiogenic switch as this proteinase makes vegf a available for the interaction with its receptors by releasing sequestered vegf a.
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a impairs the endothelial barrier by disrupting a ve cadherin/ b catenin complex via the activation of src and facilitates tumour cell extravasation and metastasis [ 136 ].
1764CDH5cadherin 5, type 2, VE-cadherin (vascular epithelium)ve cadherin1.0vegf a impairs the endothelial barrier by disrupting a ve cadherin/ b catenin complex via the activation of src and facilitates tumour cell extravasation and metastasis [ 136 ].
6207JUPjunction plakoglobincatenin1.0vegf a impairs the endothelial barrier by disrupting a ve cadherin/ b catenin complex via the activation of src and facilitates tumour cell extravasation and metastasis [ 136 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a also induces the disruption of hepatocellular tight junctions which may promote tumour invasion [ 137 ].
7176MMP9matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)mmp 91.0hiratsuka et al. [ 138 ] have shown that vegfr 1 signalling is also involved in tumour metastasis being linked to the induction of mmp 9 in lung endothelial cells and to the facilitation of lung specific metastasis.
12680VEGFAvascular endothelial growth factor Avegf a1.0transgenic mice that overexpress vegf a specifically in the epidermis exhibit an increased density of tortuous cutaneous blood capillaries as well as highly increased leucocyte rolling and adhesion in postcapillary skin venules suggesting
12680VEGFAvascular endothelial growth factor Avegf a1.0is exhibit an increased density of tortuous cutaneous blood capillaries as well as highly increased leucocyte rolling and adhesion in postcapillary skin venules suggesting that enhanced expression of vegf a in epidermal keratinocytes is sufficient to develop psoriasis like inflammatory skin lesions [ 143 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0moreover heterozygous vegf a transgenic mice which do not spontaneously develop inflammatory skin lesions are unable to down regulate experimentally induced inflammation and exhibit a psoriasis like phenotype characterized by ep
8893PGFplacental growth factorplgf 21.0transgenic overexpression of plgf 2 in epidermal keratinocytes also results in a significantly increased inflammatory response whereas a deficiency of plgf results in a diminished and abbreviated inflammatory response [ 145 ] suggestin
12680VEGFAvascular endothelial growth factor Avegf a1.0local production of vegf a in arthritic synovial tissue has been documented [ 16 ] and appears to correlate with disease activity in humans.
12680VEGFAvascular endothelial growth factor Avegf a1.0subsequently vegf a has been shown to be important in the pathogenesis of ra rheumatoid arthritis in animal models [ 146 148 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0exaggerated levels of vegf a have been detected in tissues and biological samples from people with asthma where these levels correlate directly with disease [ 149 ] and inversely with airway function [ 150 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0a recent study using lung targeted vegf 165 transgenic mice has revealed a novel function of vegf a in allergic responses.
12680VEGFAvascular endothelial growth factor Avegf a1.0in these mice vegf a induces asthma like inflammation airway and vascular remodelling and airway hyper responsiveness.
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a also enhances respiratory sensitization to antigen as well as t h 2 t helper type 2 cell mediated inflammation and increases the number of activated dendritic cells [ 151 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0thus vegf a has a critical role in pulmonary t h 2 inflammation.
12680VEGFAvascular endothelial growth factor Avegf a1.0other studies have provided evidence for a role for vegf a as a pro inflammatory mediator in allograft rejection [ 152 ] and neointimal formation [ 153 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a mrna expression not normally found in the adult mouse brain is up regulated after cerebral ischaemia and elevated vegf a levels can be detected as early as 3 h after stroke with a peak between 12 and 48 h [ 154 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0previous studies have demonstrated that the antagonism of vegf a results in reduced oedema and tissue damage after ischaemia implicating vegf a in the pathophysiology of stroke [ 155 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0paul et al. [ 156 ] have reported that src mice are resistant to vegf a induced vascular permeability and show decreased infarct volumes after stroke.
12680VEGFAvascular endothelial growth factor Avegf a1.0systemic application of a src inhibitor suppresses vascular permeability protecting wild type mice from ischaemia induced brain damage without influencing vegf a expression.
12680VEGFAvascular endothelial growth factor Avegf a1.0however sun et al. [ 157 ] have reported that intracerebroventricular administration of vegf a reduces infarct size improves neurological performance and enhances the delayed survival of newborn neurons.
12680VEGFAvascular endothelial growth factor Avegf a1.0these conflicting results appear to reflect dual roles of vegf a in stroke: neuroprotective and pro inflammatory effects.
12680VEGFAvascular endothelial growth factor Avegf a1.0in this context when infused through the internal carotid artery low and intermediate doses of vegf a significantly promote neuroprotection of the ischaemic brain whereas a high dose of vegf a offers no neuroprotection to the ischaemic brain or the damaged neurons of normal brain [ 158 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0further studies are required for the therapeutic application of vegf a against stroke.
12680VEGFAvascular endothelial growth factor Avegf a1.0a subsequent study has revealed that vegf a is a modifier associated with motor neuron degeneration in human als and in a mouse model of als [ 162 ].
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a treatment increases the life expectancy of als mice without causing toxic side effects [ 163 164 ] indicating that vegf a has neuroprotective effects on motor neurons and treatment with vegf a could be one of the most effective therapies for als reported so far.
6018IL6interleukin 6 (interferon, beta 2)interleukin 61.0the activation of vegfr 1 results in the paracrine release of hgf hepatocyte growth factor il 6 interleukin 6 and other hepatotrophic molecules by lsecs to the extent that hepatocytes are stimulated to proliferate when co cultured with lsecs.
4893HGFhepatocyte growth factor (hepapoietin A; scatter factor)hepatocyte growth factor1.0the activation of vegfr 1 results in the paracrine release of hgf hepatocyte growth factor il 6 interleukin 6 and other hepatotrophic molecules by lsecs to the extent that hepatocytes are stimulated to proliferate when co cultured with lsecs.
6018IL6interleukin 6 (interferon, beta 2)il 61.0the activation of vegfr 1 results in the paracrine release of hgf hepatocyte growth factor il 6 interleukin 6 and other hepatotrophic molecules by lsecs to the extent that hepatocytes are stimulated to proliferate when co cultured with lsecs.
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a has no direct mitogenic effect on hepatocytes.
12680VEGFAvascular endothelial growth factor Avascular endothelial growth factor1.0key words: angiogenesis inflammation signal transduction tumour vascular endothelial growth factor vegf vascular permeability.
15917PLCB1phospholipase C, beta 1 (phosphoinositide-specific)phospholipase c1.0d binding protein interacting protein 2; pdk1 phosphoinositide dependent kinase 1; pi3k phosphoinositide 3 kinase; pilsap puromycin intensive leucyl specific aminopeptidase; pkc protein kinase c; plc phospholipase c; plgf placenta growth factor; pvhl von hippel lindau tumour suppressor protein; ra rheumatoid arthritis; rtk receptor tyrosine kinase; s6k s6 kinase; tag t antigen; t h 2 t helper type 2; utr untrans
4910HIF1Ahypoxia-inducible factor 1, alpha subunit (basic helix-loop-helix transcription factor)hypoxia inducible factor 11.0abbreviations: als amyotrophic lateral sclerosis; dscr1 down syndrome critical region protein 1; ecm extracellular matrix; erk extracellular signal regulated kinase; fak focal adhesion kinase; hif 1 hypoxia inducible factor 1; hre hypoxia response element; huvec human umbilical vein endothelial cell; lsec liver sinusoidal endothelial cell; mab monoclonal antibody; mapk mitogen activated protein kinase; mmp matrix metallop
9393PRKCAprotein kinase C, alphaprotein kinase c1.0n; paip2 polyadenylated binding protein interacting protein 2; pdk1 phosphoinositide dependent kinase 1; pi3k phosphoinositide 3 kinase; pilsap puromycin intensive leucyl specific aminopeptidase; pkc protein kinase c; plc phospholipase c; plgf placenta growth factor; pvhl von hippel lindau tumour suppressor protein; ra rheumatoid arthritis; rtk receptor tyrosine kinase; s6k s6 kinase; tag t antigen; t h 2 t helpe
6879MAPK6mitogen-activated protein kinase 6extracellular signal regulated kinase1.0abbreviations: als amyotrophic lateral sclerosis; dscr1 down syndrome critical region protein 1; ecm extracellular matrix; erk extracellular signal regulated kinase; fak focal adhesion kinase; hif 1 hypoxia inducible factor 1; hre hypoxia response element; huvec human umbilical vein endothelial cell; lsec liver sinusoidal endothelial cell; mab monoclonal antibod
18420SETD2SET domain containing 2hif 11.0abbreviations: als amyotrophic lateral sclerosis; dscr1 down syndrome critical region protein 1; ecm extracellular matrix; erk extracellular signal regulated kinase; fak focal adhesion kinase; hif 1 hypoxia inducible factor 1; hre hypoxia response element; huvec human umbilical vein endothelial cell; lsec liver sinusoidal endothelial cell; mab monoclonal antibody; mapk mitogen activated protein
8893PGFplacental growth factorplacenta growth factor1.0racting protein 2; pdk1 phosphoinositide dependent kinase 1; pi3k phosphoinositide 3 kinase; pilsap puromycin intensive leucyl specific aminopeptidase; pkc protein kinase c; plc phospholipase c; plgf placenta growth factor; pvhl von hippel lindau tumour suppressor protein; ra rheumatoid arthritis; rtk receptor tyrosine kinase; s6k s6 kinase; tag t antigen; t h 2 t helper type 2; utr untranslated region; vegf vascular e
12680VEGFAvascular endothelial growth factor Avascular endothelial growth factor1.0wth factor; pvhl von hippel lindau tumour suppressor protein; ra rheumatoid arthritis; rtk receptor tyrosine kinase; s6k s6 kinase; tag t antigen; t h 2 t helper type 2; utr untranslated region; vegf vascular endothelial growth factor; vegfr vegf receptor; svegfr 1 soluble vegfr 1; svvegf snake venom vegf; tf svvegf trimeresurus flavoviridis svvegf; vpf vascular permeability factor.
12680VEGFAvascular endothelial growth factor Avascular permeability factor1.0elper type 2; utr untranslated region; vegf vascular endothelial growth factor; vegfr vegf receptor; svegfr 1 soluble vegfr 1; svvegf snake venom vegf; tf svvegf trimeresurus flavoviridis svvegf; vpf vascular permeability factor.
12680VEGFAvascular endothelial growth factor Avascular endothelial growth factor1.0the vegf vascular endothelial growth factor family and its receptors are essential regulators of angiogenesis and vascular permeability.
12680VEGFAvascular endothelial growth factor Avegf a1.0currently the vegf family consists of vegf a plgf placenta growth factor vegf b vegf c vegf d vegf e and snake venom vegf.
3708FIGFc-fos induced growth factor (vascular endothelial growth factor D)vegf d1.0currently the vegf family consists of vegf a plgf placenta growth factor vegf b vegf c vegf d vegf e and snake venom vegf.
8893PGFplacental growth factorplacenta growth factor1.0currently the vegf family consists of vegf a plgf placenta growth factor vegf b vegf c vegf d vegf e and snake venom vegf.
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a has at least nine subtypes due to the alternative splicing of a single gene.
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a binds to and activates two tyrosine kinase receptors vegfr vegf receptor 1 and vegfr 2.
12680VEGFAvascular endothelial growth factor Avegf a1.0in solid tumours vegf a and its receptor are involved in carcinogenesis invasion and distant metastasis as well as tumour angiogenesis.
12680VEGFAvascular endothelial growth factor Avegf a1.0vegf a also has a neuroprotective effect on hypoxic motor neurons and is a modifier of als amyotrophic lateral sclerosis .
12680VEGFAvascular endothelial growth factor Avascular endothelial growth factor a1.0vascular endothelial growth factor a|receptors vascular endothelial growth factor|