There is now much evidence that VEGFR-2 is the major mediator of VEGF-driven responses in endothelial cells and it is considered to be a crucial signal transducer in both physiologic and pathologic angiogenesis. The binding of VEGF to VEGFR-2 leads to a cascade of different signaling pathways, resulting in the up-regulation of genes involved in mediating the proliferation and migration of endothelial cells and promoting their survival and vascular permeability. For example, the binding of VEGF to VEGFR-2 leads to dimerization of the receptor, followed by intracellular activation of the PLCgamma;PKC-Raf kinase-MEK-mitogen-activated protein kinase (MAPK) pathway and subsequent initiation of DNA synthesis and cell growth, whereas activation of the phosphatidylinositol 3' -kinase (PI3K)-Akt pathway leads to increased endothelial-cell survival. Activation of PI3K, FAK, and p38 MAPK is implicated in cell migration signaling.

Environmental Information Processing; Signal transduction
BRITE hierarchy

Homo sapiens (human) [GN:hsa]

PMID:13678960

Cross MJ, Dixelius J, Matsumoto T, Claesson-Welsh L.

VEGF-receptor signal transduction.

Trends Biochem Sci 28:488-94 (2003)
DOI:10.1016/S0968-0004(03)00193-2

PMID:11741095

Matsumoto T, Claesson-Welsh L.

VEGF receptor signal transduction.

Sci STKE 2001:RE21 (2001)
DOI:10.1126/stke.2001.112.re21

PMID:15602010

Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA.

Vascular endothelial growth factor and angiogenesis.

Pharmacol Rev 56:549-80 (2004)
DOI:10.1124/pr.56.4.3

PMID:16104843

Takahashi H, Shibuya M.

The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions.

Clin Sci (Lond) 109:227-41 (2005)
DOI:10.1042/CS20040370

PMID:14641020

Zachary I.

VEGF signalling: integration and multi-tasking in endothelial cell biology.

Biochem Soc Trans 31:1171-7 (2003)
DOI:10.1042/bst0311171

PMID:15338053

Munoz-Chapuli R, Quesada AR, Angel Medina M.

Angiogenesis and signal transduction in endothelial cells.

Cell Mol Life Sci 61:2224-43 (2004)
DOI:10.1007/s00018-004-4070-7

PMID:14724572

Lamalice L, Houle F, Jourdan G, Huot J.

Phosphorylation of tyrosine 1214 on VEGFR2 is required for VEGF-induced activation of Cdc42 upstream of SAPK2/p38.

Oncogene 23:434-45 (2004)
DOI:10.1038/sj.onc.1207034

PMID:12391145

Shu X, Wu W, Mosteller RD, Broek D.

Sphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases.

Mol Cell Biol 22:7758-68 (2002)
DOI:10.1128/MCB.22.22.7758-7768.2002