Entry
Name
VEGF signaling pathway - Homo sapiens (human)
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
Ortholog table
Drug
D05029 Midostaurin (JAN/USAN/INN)
D05386 Pegaptanib sodium (JAN/USAN)
D06272 Sorafenib tosylate (USAN)
D06402 Sunitinib malate (JAN/USAN)
D06407 Vandetanib (JAN/USAN/INN)
D08544 Toceranib phosphate (USAN)
D08874 Bevasiranib sodium (USAN)
D08878 Brivanib alaninate (JAN/USAN/INN)
D08883 Cediranib maleate (JAN/USAN)
D08947 Motesanib diphosphate (USAN)
D09603 Dilmapimod tosylate (USAN)
D09665 Saracatinib difumarate (USAN)
D09920 Lenvatinib mesylate (USAN)
D09945 Pegdinetanib (USAN/INN)
D10095 Cabozantinib s-malate (USAN)
D10137 Regorafenib hydrate (JAN)
D10190 Tivozanib hydrochloride (USAN)
D10396 Nintedanib esylate (USAN)
D10465 Golvatinib tartrate (USAN)
D10486 Pimasertib hydrochloride (USAN)
D11083 Brolucizumab (USAN/INN)
D11126 Navicixizumab (USAN/INN)
D11289 Rivoceranib mesylate (USAN)
D11517 Abicipar pegol (USAN/INN)
D12508 Tarcocimab tedromer (INN)
Other DBs
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
7422 VEGFA; vascular endothelial growth factor A [KO:K05448 ]
3265 HRAS; HRas proto-oncogene, GTPase [KO:K02833 ]
3845 KRAS; KRAS proto-oncogene, GTPase [KO:K07827 ]
4893 NRAS; NRAS proto-oncogene, GTPase [KO:K07828 ]
5534 PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268 ]
5535 PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268 ]
4773 NFATC2; nuclear factor of activated T cells 2 [KO:K17332 ]
998 CDC42; cell division cycle 42 [KO:K04393 ]
3315 HSPB1; heat shock protein family B (small) member 1 [KO:K04455 ]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
572 BAD; BCL2 associated agonist of cell death [KO:K02158 ]
Compound
C01245 D-myo-Inositol 1,4,5-trisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Cross MJ, Dixelius J, Matsumoto T, Claesson-Welsh L.
Title
VEGF-receptor signal transduction.
Journal
Reference
Authors
Matsumoto T, Claesson-Welsh L.
Title
VEGF receptor signal transduction.
Journal
Reference
Authors
Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA.
Title
Vascular endothelial growth factor and angiogenesis.
Journal
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
Reference
Authors
Zachary I.
Title
VEGF signalling: integration and multi-tasking in endothelial cell biology.
Journal
Reference
Authors
Munoz-Chapuli R, Quesada AR, Angel Medina M.
Title
Angiogenesis and signal transduction in endothelial cells.
Journal
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
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
Related pathway
KO pathway