KEGG   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
hsa04370

Drug
D03218  Axitinib (JAN/USAN)
D03658  Dasatinib (JAN/INN)
D03736  Doramapimod (USAN/INN)
D05029  Midostaurin (JAN/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)
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)
D09589  Brivanib (USAN)
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)
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)
D11083  Brolucizumab (USAN/INN)
D11126  Navicixizumab (USAN/INN)
D11244  Vanucizumab (USAN/INN)
D11288  Rivoceranib (USAN/INN)
D11289  Rivoceranib mesylate (USAN)
D11517  Abicipar pegol (USAN/INN)
D11642  Dilpacimab (USAN/INN)
D11890  Emvododstat (USAN)
D12237  Zunsemetinib (USAN)
D12507  Tarcocimab (INN)
D12508  Tarcocimab tedromer (INN)
D12560  Gamcemetinib (USAN)
D12808  Ivonescimab (USAN/INN)
Other DBs
GO: 0048010
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]
100137049  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; MAPK activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
7867  MAPKAPK3; MAPK 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
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)
DOI:10.1016/S0968-0004(03)00193-2
Reference
PMID:11741095
  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
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)
DOI:10.1124/pr.56.4.3
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)
DOI:10.1042/CS20040370
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)
DOI:10.1042/bst0311171
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)
DOI:10.1007/s00018-004-4070-7
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)
DOI:10.1038/sj.onc.1207034
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)
DOI:10.1128/MCB.22.22.7758-7768.2002
Related
pathway
hsa00590  Arachidonic acid metabolism
hsa04010  MAPK signaling pathway
hsa04020  Calcium signaling pathway
hsa04151  PI3K-Akt signaling pathway
hsa04510  Focal adhesion
KO pathway
ko04370   

  All links  
Genome (1)   
   KEGG GENOME (1)   
Gene (59)   
   KEGG GENES (59)   
All databases (60)   

Download RDF
DBGET integrated database retrieval system