KEGG   PATHWAY: hsa04370Help
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
BRITE hierarchy
Pathway map
VEGF signaling pathway
hsa04370

All organismsOrtholog table
Disease
H01482  
Infantile hemangioma
H01529  
Avascular necrosis of femoral head
Drug
D00109  
Aspirin (JP17/USP)
D00118  
Naproxen (JP17/USP/INN)
D00120  
Sulindac (JP17/USP/INN)
D00126  
Ibuprofen (JP17/USP/INN)
D00127  
Piroxicam (JP17/USP/INN)
D00130  
Diflunisal (JAN/USP/INN)
D00132  
Ketoprofen (JP17/USP/INN)
D00141  
Indomethacin (USP)
D00151  
Mefenamic acid (JP17/USP/INN)
D00158  
Tolmetin sodium (JAN/USP)
D00315  
Etodolac (JP17/USP/INN)
D00330  
Flurbiprofen (JP17/USP/INN)
D00428  
Salsalate (USP/INN)
D00463  
Oxaprozin (JP17/USAN/INN)
D00510  
Phenylbutazone (JP17/USP/INN)
D00566  
Sodium salicylate (JP17/USP)
D00567  
Celecoxib (JAN/USAN/INN)
D03218  
Axitinib (JAN/USAN)
D03658  
Dasatinib (INN)
D03736  
Doramapimod (USAN/INN)
D05386  
Pegaptanib sodium (JAN/USAN)
D05697  
Ranibizumab (USAN/INN)
D05819  
Semaxanib (USAN/INN)
D06272  
Sorafenib tosylate (USAN)
D06285  
Vatalanib (USAN/INN)
D06402  
Sunitinib malate (JAN/USAN)
D06407  
Vandetanib (JAN/USAN/INN)
D06409  
Bevacizumab (USAN)
D06414  
Dasatinib (USAN)
D06678  
Motesanib
D07269  
Dexketoprofen (INN)
D08103  
Ketoprofen 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 diphosphate (USAN)
D08963  
Pamapimod (INN/USAN)
D09371  
Ramucirumab (USAN)
D09386  
Talmapimod (USAN/INN)
D09574  
Aflibercept (USAN/INN)
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)
D09919  
Lenvatinib (USAN/INN)
D09920  
Lenvatinib mesylate (USAN)
D09945  
Pegdinetanib (USAN/INN)
D10017  
Naproxen etemesil (USAN)
D10062  
Cabozantinib (USAN)
D10095  
Cabozantinib s-malate (USAN)
D10137  
Regorafenib hydrate (JAN)
D10138  
Regorafenib (USAN/INN)
D10190  
Tivozanib hydrochloride (USAN)
D10224  
Golvatinib (USAN)
D10396  
Nintedanib esylate (USAN)
D10426  
Pimasertib (USAN/INN)
D10465  
Golvatinib tartrate (USAN)
D10481  
Nintedanib (USAN/INN)
D10486  
Pimasertib hydrochloride (USAN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
7422  
VEGFA; vascular endothelial growth factor A [KO:K05448]
3791  
KDR; kinase insert domain receptor [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 [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:K19662] [EC:2.7.11.13]
5582  
PRKCG; protein kinase C gamma [KO:K19663] [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; HRas proto-oncogene, GTPase [KO:K02833]
3845  
KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
4893  
NRAS; NRAS proto-oncogene, GTPase [KO:K07828]
5894  
RAF1; Raf-1 proto-oncogene, serine/threonine kinase [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 [KO:K16342] [EC:3.1.1.4]
8681  
JMJD7-PLA2G4B; JMJD7-PLA2G4B readthrough [KO:K16342] [EC:3.1.1.4]
PLA2G4B; phospholipase A2 group IVB [KO:K16342] [EC:3.1.1.4]
8605  
PLA2G4C; phospholipase A2 group IVC [KO:K16342] [EC:3.1.1.4]
283748  
PLA2G4D; phospholipase A2 group IVD [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 [KO:K04348] [EC:3.1.3.16]
5532  
PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
5533  
PPP3CC; protein phosphatase 3 catalytic subunit gamma [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]
4773  
NFATC2; nuclear factor of activated T cells 2 [KO:K17332]
5743  
PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
5747  
PTK2; protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
25759  
SHC2; SHC adaptor protein 2 [KO:K17447]
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 protein family B (small) member 1 [KO:K04455]
6714  
SRC; SRC proto-oncogene, non-receptor tyrosine kinase [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]
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]
5879  
RAC1; Rac family small GTPase 1 [KO:K04392]
5880  
RAC2; Rac family small GTPase 2 [KO:K07860]
5881  
RAC3; Rac family small GTPase 3 [KO:K07861]
207  
AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
208  
AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
10000  
AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
4846  
NOS3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
842  
CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
572  
BAD; BCL2 associated agonist of cell death [KO:K02158]
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
  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
KO pathway
 

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