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 transductionBRITE hierarchy
Pathway map 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)
D11083 Brolucizumab (USAN/INN)
D11126 Navicixizumab (USAN/INN)
D11289 Rivoceranib mesylate (USAN)
D11517 Abicipar pegol (USAN/INN)
D12508 Tarcocimab tedromer (INN)
D13058 Migaldendranib (USAN/INN)
D13256 Cabozantinib laurylsulfate (USAN)
Other DBs Organism Homo sapiens (human) [GN:
hsa ]
Gene 208 AKT2; RAC-beta serine/threonine-protein kinase isoform 1 [KO:K04456 ] [EC:2.7.11.1 ]
25759 SHC2; SHC-transforming protein 2 isoform 1 [KO:K17447 ]
3791 KDR; vascular endothelial growth factor receptor 2 precursor [KO:K05098 ] [EC:2.7.10.1 ]
4773 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform C [KO:K17332 ]
5290 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1 [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform 1 [KO:K00922 ] [EC:2.7.1.153 ]
5295 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform 1 [KO:K02649 ]
5296 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
5335 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform b [KO:K01116 ] [EC:3.1.4.11 ]
5336 PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859 ] [EC:3.1.4.11 ]
5530 PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform 1 [KO:K04348 ] [EC:3.1.3.16 ]
5532 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform b [KO:K04348 ] [EC:3.1.3.16 ]
5533 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform 2 [KO:K04348 ] [EC:3.1.3.16 ]
5534 PPP3R1; calcineurin subunit B type 1 [KO:K06268 ]
5535 PPP3R2; calcineurin subunit B type 2 [KO:K06268 ]
5604 MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform 1 [KO:K04368 ] [EC:2.7.12.2 ]
5605 MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform 1 [KO:K04369 ] [EC:2.7.12.2 ]
572 BAD; bcl2-associated agonist of cell death [KO:K02158 ]
5879 RAC1; ras-related C3 botulinum toxin substrate 1 isoform Rac1 [KO:K04392 ]
5880 RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860 ]
5881 RAC3; ras-related C3 botulinum toxin substrate 3 isoform 1 [KO:K07861 ]
5894 RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform b [KO:K04366 ] [EC:2.7.11.1 ]
7422 VEGFA; vascular endothelial growth factor A, long form isoform b [KO:K05448 ]
8503 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform 1 [KO:K02649 ]
8605 PLA2G4C; cytosolic phospholipase A2 gamma isoform 1 precursor [KO:K16342 ] [EC:3.1.1.4 ]
9047 SH2D2A; SH2 domain-containing protein 2A isoform 2 [KO:K08273 ]
998 CDC42; cell division control protein 42 homolog isoform 1 precursor [KO:K04393 ]
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 KO pathway
