KEGG PATHWAY: hsa04370

PATHWAY: hsa04370

Entry

hsa04370 Pathway

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

Pathway map

hsa04370

VEGF signaling pathway

Disease

H00539	PTEN hamartoma tumor syndrome (PHTS)
H00856	Distal hereditary motor neuropathies (dHMN)

Drug

D00109	Aspirin (JP16/USP)
D00118	Naproxen (JP16/USP/INN)
D00120	Sulindac (JP16/USP/INN)
D00126	Ibuprofen (JP16/USP/INN)
D00127	Piroxicam (JP16/USP/INN)
D00130	Diflunisal (JAN/USP/INN)
D00132	Ketoprofen (JP16/USP/INN)
D00141	Indometacin (JP16/INN)
D00151	Mefenamic acid (JP16/USP/INN)
D00158	Tolmetin sodium (JAN/USP)
D00169	Meclofenamate sodium (USP)
D00315	Etodolac (JP16/USP/INN)
D00330	Flurbiprofen (JP16/USP/INN)
D00425	Nabumetone (JP16/USP/INN)
D00428	Sasapyrine (JAN)
D00463	Oxaprozin (JP16/USAN/INN)
D00510	Phenylbutazone (JP16/USP/INN)
D00566	Sodium salicylate (JP16/USP)
D00567	Celecoxib (JAN/USAN/INN)
D00568	Rofecoxib (JAN/USAN/INN)
D03218	Axitinib (JAN/USAN)
D03252	Bosutinib (USAN)
D03658	Dasatinib (INN)
D03736	Doramapimod (USAN/INN)
D05386	Pegaptanib sodium (JAN/USAN)
D05697	Ranibizumab (genetical recombination) (JAN)
D05819	Semaxanib (USAN/INN)
D06272	Sorafenib tosilate (JAN)
D06285	Vatalanib (USAN/INN)
D06402	Sunitinib malate (JAN/USAN)
D06407	Vandetanib (JAN/USAN/INN)
D06409	Bevacizumab (genetical recombination) (JAN)
D06414	Dasatinib hydrate (JAN)
D06678	Motesanib
D07269	Dexketoprofen (INN)
D08103	Ketoprofen sodium
D08162	Meclofenamate sodium
D08374	Piketoprofen (INN)
D08375	Piketoprofen hydrochloride
D08503	Toceranib (USAN)
D08524	Sorafenib (USAN/INN)
D08544	Toceranib phosphate (USAN)
D08552	Sunitinib (INN)
D08874	Bevasiranib sodium (USAN)
D08878	Brivanib alaninate (JAN/USAN/INN)
D08881	Cediranib (USAN/INN)
D08883	Cediranib maleate (JAN/USAN)
D08947	Motesanib phosphate (JAN)
D08963	Pamapimod (INN/USAN)
D09371	Ramucirumab (USAN)
D09386	Talmapimod (USAN/INN)
D09574	Aflibercept (genetical recombination) (JAN)
D09602	Dilmapimod (USAN/INN)
D09603	Dilmapimod tosylate (USAN)
D09618	Foretinib (USAN/INN)
D09635	Linifanib (USAN/INN)
D09639	Losmapimod (USAN/INN)
D09664	Saracatinib (USAN/INN)
D09665	Saracatinib difumarate (USAN)
D09683	Tivozanib (USAN/INN)
D09728	Bosutinib hydrate (JAN)
D09945	Pegdinetanib (USAN/INN)
D10017	Naproxen etemesil (USAN)
D10062	Cabozantinib (USAN)
D10190	Tivozanib hydrochloride (USAN)
D10224	Golvatinib (USAN)

Other DBs

BSID:

83066

GO:

0048010

Organism

Homo sapiens (human) [GN:hsa]

Gene

7422	VEGFA; vascular endothelial growth factor A [KO:K05448]
3791	KDR; kinase insert domain receptor (a type III receptor tyrosine kinase) [KO:K05098] [EC:2.7.10.1]
9047	SH2D2A; SH2 domain containing 2A [KO:K08273]
5335	PLCG1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
5336	PLCG2; phospholipase C, gamma 2 (phosphatidylinositol-specific) [KO:K05859] [EC:3.1.4.11]
5578	PRKCA; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
5579	PRKCB; protein kinase C, beta [KO:K02677] [EC:2.7.11.13]
5582	PRKCG; protein kinase C, gamma [KO:K02677] [EC:2.7.11.13]
8877	SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
56848	SPHK2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
3265	HRAS; v-Ha-ras Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845	KRAS; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
4893	NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
5894	RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [KO:K04366] [EC:2.7.11.1]
5604	MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605	MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594	MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595	MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
123745	PLA2G4E; phospholipase A2, group IVE [KO:K16342] [EC:3.1.1.4]
5321	PLA2G4A; phospholipase A2, group IVA (cytosolic, calcium-dependent) [KO:K16342] [EC:3.1.1.4]
8681	JMJD7-PLA2G4B; JMJD7-PLA2G4B readthrough [KO:K16342] [EC:3.1.1.4]
100137049	PLA2G4B; phospholipase A2, group IVB (cytosolic) [KO:K16342] [EC:3.1.1.4]
8605	PLA2G4C; phospholipase A2, group IVC (cytosolic, calcium-independent) [KO:K16342] [EC:3.1.1.4]
283748	PLA2G4D; phospholipase A2, group IVD (cytosolic) [KO:K16342] [EC:3.1.1.4]
255189	PLA2G4F; phospholipase A2, group IVF [KO:K16342] [EC:3.1.1.4]
5530	PPP3CA; protein phosphatase 3, catalytic subunit, alpha isozyme [KO:K04348] [EC:3.1.3.16]
5532	PPP3CB; protein phosphatase 3, catalytic subunit, beta isozyme [KO:K04348] [EC:3.1.3.16]
5533	PPP3CC; protein phosphatase 3, catalytic subunit, gamma isozyme [KO:K04348] [EC:3.1.3.16]
5534	PPP3R1; protein phosphatase 3, regulatory subunit B, alpha [KO:K06268]
5535	PPP3R2; protein phosphatase 3, regulatory subunit B, beta [KO:K06268]
11261	CHP1; calcineurin-like EF-hand protein 1 [KO:K06268]
63928	CHP2; calcineurin-like EF-hand protein 2 [KO:K06268]
4776	NFATC4; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4 [KO:K04446]
4772	NFATC1; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 [KO:K04446]
10725	NFAT5; nuclear factor of activated T-cells 5, tonicity-responsive [KO:K04446]
4773	NFATC2; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2 [KO:K04446]
4775	NFATC3; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3 [KO:K04446]
5743	PTGS2; prostaglandin-endoperoxide synthase 2 (prostaglandin G/H synthase and cyclooxygenase) [KO:K11987] [EC:1.14.99.1]
5747	PTK2; protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
5829	PXN; paxillin [KO:K05760]
998	CDC42; cell division cycle 42 [KO:K04393]
5600	MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300	MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603	MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432	MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
9261	MAPKAPK2; mitogen-activated protein kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
7867	MAPKAPK3; mitogen-activated protein kinase-activated protein kinase 3 [KO:K04444] [EC:2.7.11.1]
3315	HSPB1; heat shock 27kDa protein 1 [KO:K04455]
6714	SRC; v-src sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (avian) [KO:K05704] [EC:2.7.10.2]
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]
5294	PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
5295	PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
23533	PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
5296	PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
8503	PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [KO:K02649]
5879	RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
5880	RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
5881	RAC3; ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [KO:K07861]
207	AKT1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
208	AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
10000	AKT3; v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma) [KO:K04456] [EC:2.7.11.1]
842	CASP9; caspase 9, apoptosis-related cysteine peptidase [KO:K04399] [EC:3.4.22.62]
572	BAD; BCL2-associated agonist of cell death [KO:K02158]
25759	SHC2; SHC (Src homology 2 domain containing) transforming protein 2 [KO:K06279]
4846	NOS3; nitric oxide synthase 3 (endothelial cell) [KO:K13242] [EC:1.14.13.39]

Compound

C00076	Calcium cation
C00165	Diacylglycerol
C00533	Nitric oxide
C01245	D-myo-Inositol 1,4,5-trisphosphate
C01312	Prostaglandin I2
C05981	Phosphatidylinositol-3,4,5-trisphosphate

Reference

PMID:13678960

Authors

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

Title

VEGF-receptor signal transduction.

Journal

Trends Biochem Sci 28:488-94 (2003)

Reference

PMID:11741095

Authors

Matsumoto T, Claesson-Welsh L.

Title

VEGF receptor signal transduction.

Journal

Sci STKE 2001:RE21 (2001)

Reference

PMID:15602010

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)

Reference

PMID:16104843

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)

Reference

PMID:14641020

Authors

Zachary I.

Title

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

Journal

Biochem Soc Trans 31:1171-7 (2003)

Reference

PMID:15338053

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)

Reference

PMID:14724572

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)

Reference

PMID:12391145

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)

KO pathway

ko04370

All links

Ontology (2)   
   KEGG BRITE (2)   
Pathway (1)   
   BioSystems (1)   
Disease (2)   
   KEGG DISEASE (2)   
Drug (66)   
   KEGG DRUG (66)   
Genome (1)   
   KEGG GENOME (1)   
Gene (67)   
   KEGG GENES (67)   
All databases (139)   

Download RDF

DBGET integrated database retrieval system