Signaling by VEGF (Homo sapiens)

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1-44, 521-2514-16, 19, 206, 8, 13-18266-12cytosolNRP-1VEGFR3VEGFA,C,D,EVEGFA,B,PLGFVEGFR1VEGF homodimerVEGF-C,DVEGFR2VEGFR3:VEGF-C, and DVEGF-A variant4/VEGF165VEGFNRP-2VEGFR1:VEGFA,B,PGLFNRP-2:VEGFR1NRP1:VERGF165:VERGFR2VEGFR2:VEGFA,C,D,E


Description

In normal development vascular endothelial growth factors (VEGFs) are crucial regulators of vascular development during embryogenesis (vasculogenesis) and blood-vessel formation in the adult (angiogenesis). In tumor progression, activation of VEGF pathways promotes tumor vascularization, facilitating tumor growth and metastasis. Abnormal VEGF function is also associated with inflammatory diseases including atherosclerosis, and hyperthyroidism. The members of the VEGF and VEGF-receptor protein families have distinct but overlapping ligand-receptor specificities, cell-type expression, and function. VEGF-receptor activation in turn regulates a network of signaling processes in the body that promote endothelial cell growth, migration and survival (Hicklin and Ellis, 2005; Shibuya and Claesson-Welsh, 2006).
Molecular features of the VGF signaling cascades are outlined in the figure below (from Olsson et al. 2006; Nature Publishing Group). Tyrosine residues in the intracellular domains of VEGF receptors 1, 2,and 3 are indicated by dark blue boxes; residues susceptible to phosphorylation are numbered. A circled R indicates that phosphorylation is regulated by cell state (VEGFR2), by ligand binding (VEGFR1), or by heterodimerization (VEGFR3). Specific phosphorylation sites (boxed numbers) bind signaling molecules (dark blue ovals), whose interaction with other cytosolic signaling molecules (light blue ovals) leads to specific cellular (pale blue boxes) and tissue-level (pink boxes) responses in vivo. Signaling cascades whose molecular details are unclear are indicated by dashed arrows. DAG, diacylglycerol; EC, endothelial cell; eNOS, endothelial nitric oxide synthase; FAK, focal adhesion kinase; HPC, hematopoietic progenitor cell; HSP27, heat-shock protein-27; MAPK, mitogen-activated protein kinase; MEK, MAPK and ERK kinase; PI3K, phosphatidylinositol 3' kinase; PKC, protein kinase C; PLCgamma, phospholipase C-gamma; Shb, SH2 and beta-cells; TSAd, T-cell-specific adaptor.
In the current release, the first events in these cascades - the interactions between VEGF proteins and their receptors - are annotated. Details of signaling events and their biological outcome, concisely illustrated in the image below, will be available in future versions of this pathway.

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History

View all...
CompareRevisionActionTimeUserComment
114739view16:22, 25 January 2021ReactomeTeamReactome version 75
113183view11:25, 2 November 2020ReactomeTeamReactome version 74
112411view15:35, 9 October 2020ReactomeTeamReactome version 73
101315view11:20, 1 November 2018ReactomeTeamreactome version 66
100852view20:52, 31 October 2018ReactomeTeamreactome version 65
100393view19:26, 31 October 2018ReactomeTeamreactome version 64
99941view16:10, 31 October 2018ReactomeTeamreactome version 63
99497view14:44, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99146view12:41, 31 October 2018ReactomeTeamreactome version 62
94010view13:51, 16 August 2017ReactomeTeamreactome version 61
93733view13:24, 16 August 2017ReactomeTeamreactome version 61
93731view12:48, 16 August 2017ReactomeTeamreactome version 61
93629view11:29, 9 August 2017ReactomeTeamreactome version 61
86740view09:25, 11 July 2016ReactomeTeamreactome version 56
83276view10:37, 18 November 2015ReactomeTeamVersion54
81395view12:55, 21 August 2015ReactomeTeamVersion53
76864view08:13, 17 July 2014ReactomeTeamFixed remaining interactions
76569view11:55, 16 July 2014ReactomeTeamFixed remaining interactions
75902view09:55, 11 June 2014ReactomeTeamRe-fixing comment source
75603view10:45, 10 June 2014ReactomeTeamReactome 48 Update
74958view13:48, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74602view08:39, 30 April 2014ReactomeTeamReactome46
69045view17:53, 8 July 2013MaintBotUpdated to 2013 gpml schema
45208view17:19, 7 October 2011KhanspersOntology Term : 'VEGF signaling pathways' added !
42135view21:59, 4 March 2011MaintBotAutomatic update
39945view05:57, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
NRP-1 ProteinREACT_12698 (Reactome)
NRP-2 ProteinREACT_13365 (Reactome)
NRP-2:VEGFR1 ComplexREACT_13266 (Reactome)
NRP1:VERGF165:

VERGFR2

ComplexREACT_12681 (Reactome)
VEGF ProteinREACT_12955 (Reactome)
VEGF homodimer ComplexREACT_12721 (Reactome)
VEGF-A

variant4/VEGF165

ProteinP15692-4 (UniProt)
VEGF-C,D ComplexREACT_12875 (Reactome)
VEGFA,B,PLGF ComplexREACT_12921 (Reactome)
VEGFA,C,D,E ComplexREACT_12894 (Reactome)
VEGFR1 ProteinREACT_12746 (Reactome)
VEGFR1:VEGFA,B,

PGLF

ComplexREACT_12847 (Reactome)
VEGFR2 ProteinP35968 (UniProt)
VEGFR2:VEGFA,C,D,

E

ComplexREACT_13060 (Reactome)
VEGFR3 ProteinP35916 (UniProt)
VEGFR3:VEGF-C,

and D

ComplexREACT_12751 (Reactome)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP1919"
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