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
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 (genetical recombination) (JAN)
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)
D10426  
Pimasertib (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 (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; Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845  
KRAS; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
4893  
NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [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 (cytosolic, calcium-dependent) [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 (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]
4773  
NFATC2; nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2 [KO:K17332]
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]
25759  
SHC2; SHC (Src homology 2 domain containing) transforming 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 27kDa protein 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]
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 [KO:K04456] [EC:2.7.11.1]
4846  
NOS3; nitric oxide synthase 3 (endothelial cell) [KO:K13242] [EC:1.14.13.39]
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]
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)
Reference
  Authors
Matsumoto T, Claesson-Welsh L.
  Title
VEGF receptor signal transduction.
  Journal
Sci STKE 2001:RE21 (2001)
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)
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)
Reference
  Authors
Zachary I.
  Title
VEGF signalling: integration and multi-tasking in endothelial cell biology.
  Journal
Biochem Soc Trans 31:1171-7 (2003)
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)
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)
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)
KO pathway
 

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