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Entry
map04370                    Pathway                                

Name
VEGF signaling pathway
Description
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.
Class
Environmental Information Processing; Signal transduction
BRITE hierarchy
Pathway map
VEGF signaling pathway
map04370

All organismsOrtholog table
Disease
H00539  
PTEN hamartoma tumor syndrome (PHTS)
H01482  
Infantile hemangioma
H01529  
Avascular necrosis of femoral head
Other DBs
GO: 
Reference
  Authors
Cross MJ, Dixelius J, Matsumoto T, Claesson-Welsh L.
  Title
VEGF-receptor signal transduction.
  Journal
Trends Biochem Sci 28:488-94 (2003)
DOI:10.1016/S0968-0004(03)00193-2
Reference
  Authors
Matsumoto T, Claesson-Welsh L.
  Title
VEGF receptor signal transduction.
  Journal
Sci STKE 2001:RE21 (2001)
DOI:10.1126/stke.2001.112.re21
Reference
  Authors
Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA.
  Title
Vascular endothelial growth factor and angiogenesis.
  Journal
Pharmacol Rev 56:549-80 (2004)
DOI:10.1124/pr.56.4.3
Reference
  Authors
Takahashi H, Shibuya M.
  Title
The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions.
  Journal
Clin Sci (Lond) 109:227-41 (2005)
DOI:10.1042/CS20040370
Reference
  Authors
Zachary I.
  Title
VEGF signalling: integration and multi-tasking in endothelial cell biology.
  Journal
Biochem Soc Trans 31:1171-7 (2003)
DOI:10.1042/bst0311171
Reference
  Authors
Munoz-Chapuli R, Quesada AR, Angel Medina M.
  Title
Angiogenesis and signal transduction in endothelial cells.
  Journal
Cell Mol Life Sci 61:2224-43 (2004)
DOI:10.1007/s00018-004-4070-7
Reference
  Authors
Lamalice L, Houle F, Jourdan G, Huot J.
  Title
Phosphorylation of tyrosine 1214 on VEGFR2 is required for VEGF-induced activation of Cdc42 upstream of SAPK2/p38.
  Journal
Oncogene 23:434-45 (2004)
DOI:10.1038/sj.onc.1207034
Reference
  Authors
Shu X, Wu W, Mosteller RD, Broek D.
  Title
Sphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases.
  Journal
Mol Cell Biol 22:7758-68 (2002)
DOI:10.1128/MCB.22.22.7758-7768.2002
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