KEGG   PATHWAY: cge04370
Entry
cge04370                    Pathway                                
Name
VEGF signaling pathway - Cricetulus griseus (Chinese hamster)
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
cge04370  VEGF signaling pathway
cge04370

Other DBs
GO: 0048010
Organism
Cricetulus griseus (Chinese hamster) [GN:cge]
Gene
100755957  Vegfa; LOW QUALITY PROTEIN: vascular endothelial growth factor A isoform X2 [KO:K05448]
100756294  Kdr; vascular endothelial growth factor receptor 2 isoform X2 [KO:K05098] [EC:2.7.10.1]
100751565  Sh2d2a; SH2 domain-containing protein 2A isoform X1 [KO:K08273]
100769697  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116] [EC:3.1.4.11]
100752475  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
100766006  Prkca; protein kinase C alpha type isoform X2 [KO:K02677] [EC:2.7.11.13]
100760922  Prkcb; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
100762950  Prkcg; protein kinase C gamma type isoform X2 [KO:K19663] [EC:2.7.11.13]
100762053  Sphk1; sphingosine kinase 1 isoform X1 [KO:K04718] [EC:2.7.1.91]
100774790  Sphk2; sphingosine kinase 2 isoform X2 [KO:K04718] [EC:2.7.1.91]
100773737  Hras; GTPase HRas isoform X2 [KO:K02833]
100763178  Kras; GTPase KRas isoform X4 [KO:K07827]
113839127  GTPase KRas-like [KO:K07827]
113837935  GTPase KRas-like isoform X2 [KO:K07827]
113837956  GTPase KRas-like [KO:K07827]
113838653  GTPase KRas-like isoform X2 [KO:K07827]
113838692  GTPase KRas-like [KO:K07827]
113838722  GTPase KRas-like isoform X1 [KO:K07827]
113838818  GTPase KRas-like [KO:K07827]
113837633  GTPase KRas-like isoform X1 [KO:K07827]
113838146  GTPase KRas-like isoform X1 [KO:K07827]
113838876  GTPase KRas-like [KO:K07827]
113838228  GTPase KRas-like isoform X1 [KO:K07827]
113839011  GTPase KRas-like [KO:K07827]
100771078  GTPase KRas-like isoform X2 [KO:K07827]
113837960  GTPase KRas-like [KO:K07827]
113838098  GTPase KRas-like [KO:K07827]
113838326  GTPase KRas-like [KO:K07827]
113838417  GTPase KRas-like isoform X1 [KO:K07827]
113838488  GTPase KRas-like [KO:K07827]
113838583  GTPase KRas-like isoform X1 [KO:K07827]
113838676  GTPase KRas-like [KO:K07827]
113838679  GTPase KRas-like isoform X1 [KO:K07827]
113838746  GTPase KRas-like [KO:K07827]
113838796  GTPase KRas-like isoform X1 [KO:K07827]
113838871  GTPase KRas-like [KO:K07827]
113838872  GTPase KRas-like [KO:K07827]
113838892  GTPase KRas-like [KO:K07827]
113838898  GTPase KRas-like [KO:K07827]
113838914  GTPase KRas-like [KO:K07827]
113838921  GTPase KRas-like [KO:K07827]
113838942  GTPase KRas-like isoform X1 [KO:K07827]
113838943  GTPase KRas-like isoform X1 [KO:K07827]
113839007  GTPase HRas-like isoform X1 [KO:K07827]
118239746  GTPase KRas-like isoform X1 [KO:K07827]
118239767  GTPase KRas-like isoform X1 [KO:K07827]
118239768  GTPase KRas-like [KO:K07827]
118239770  GTPase KRas-like [KO:K07827]
118239801  GTPase KRas-like [KO:K07827]
118239825  GTPase KRas-like isoform X1 [KO:K07827]
100757614  Nras; GTPase NRas [KO:K07828]
100769018  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
100689403  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
113835540  dual specificity mitogen-activated protein kinase kinase 1-like isoform X1 [KO:K04368] [EC:2.7.12.2]
103158537  dual specificity mitogen-activated protein kinase kinase 1-like isoform X2 [KO:K04368] [EC:2.7.12.2]
100774204  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 isoform X2 [KO:K04369] [EC:2.7.12.2]
100759514  Mapk1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
100753149  Mapk3; mitogen-activated protein kinase 3 isoform X2 [KO:K04371] [EC:2.7.11.24]
100750927  Pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
100770894  Pla2g4e; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
100771756  Pla2g4b; cytosolic phospholipase A2 beta isoform X1 [KO:K16342] [EC:3.1.1.4]
100770605  Pla2g4f; cytosolic phospholipase A2 zeta isoform X3 [KO:K16342] [EC:3.1.1.4]
100754559  Pla2g4c; cytosolic phospholipase A2 gamma isoform X2 [KO:K16342] [EC:3.1.1.4]
103158591  Pla2g4d; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
100751412  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X6 [KO:K04348] [EC:3.1.3.16]
100752571  serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
100764987  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
100754314  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
100773706  Ppp3r1; calcineurin subunit B type 1 isoform X2 [KO:K06268]
100762227  Nfatc2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X2 [KO:K17332]
100751220  Ptgs2; prostaglandin G/H synthase 2 [KO:K11987] [EC:1.14.99.1]
100759464  Ptk2; focal adhesion kinase 1 isoform X5 [KO:K05725] [EC:2.7.10.2]
100761269  Shc2; LOW QUALITY PROTEIN: SHC-transforming protein 2 [KO:K17447]
100760740  Pxn; paxillin isoform X1 [KO:K05760]
100765433  Cdc42; cell division control protein 42 homolog [KO:K04393]
100689104  Mapk14; mitogen-activated protein kinase 14 isoform X3 [KO:K04441] [EC:2.7.11.24]
100759172  Mapk11; mitogen-activated protein kinase 11 isoform X2 [KO:K04441] [EC:2.7.11.24]
100754042  Mapk12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
100763519  Mapk13; mitogen-activated protein kinase 13 isoform X2 [KO:K04441] [EC:2.7.11.24]
100762218  Mapkapk2; MAP kinase-activated protein kinase 2 isoform X2 [KO:K04443] [EC:2.7.11.1]
100774379  Mapkapk3; MAP kinase-activated protein kinase 3 [KO:K04444] [EC:2.7.11.1]
100763481  Hspb1; heat shock protein beta-1 isoform X2 [KO:K04455]
100757188  Src; proto-oncogene tyrosine-protein kinase Src isoform X2 [KO:K05704] [EC:2.7.10.2]
100689251  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100769225  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
100689252  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
100771181  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X2 [KO:K02649]
100750761  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100774067  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100756792  Rac1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
113837706  ras-related C3 botulinum toxin substrate 1-like [KO:K04392]
100767225  ras-related C3 botulinum toxin substrate 2 isoform X2 [KO:K07860]
100757479  Rac3; ras-related C3 botulinum toxin substrate 3 isoform X2 [KO:K07861]
100768351  Akt2; RAC-beta serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
100752454  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100769460  Akt1; RAC-alpha serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
100769961  Nos3; nitric oxide synthase, endothelial isoform X3 [KO:K13242] [EC:1.14.13.39]
103160479  caspase-9-like [KO:K04399] [EC:3.4.22.62]
100689370  caspase-9 [KO:K04399] [EC:3.4.22.62]
113833881  caspase-9-like [KO:K04399] [EC:3.4.22.62]
100760426  Bad; bcl2-associated agonist of cell death isoform X2 [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
cge00590  Arachidonic acid metabolism
cge04010  MAPK signaling pathway
cge04020  Calcium signaling pathway
cge04151  PI3K-Akt signaling pathway
cge04510  Focal adhesion
KO pathway
ko04370   
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