KEGG   PATHWAY: amj04370
Entry
amj04370                    Pathway                                
Name
VEGF signaling pathway - Alligator mississippiensis (American alligator)
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
amj04370  VEGF signaling pathway
amj04370

Other DBs
GO: 0048010
Organism
Alligator mississippiensis (American alligator) [GN:amj]
Gene
102576555  VEGFA; vascular endothelial growth factor A [KO:K05448]
102567818  KDR; kinase insert domain receptor [KO:K05098] [EC:2.7.10.1]
102572591  SH2D2A; SH2 domain containing 2A [KO:K08273]
102574067  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
102563626  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
106736910  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
102572836  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
102572486  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
102574559  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
102558563  SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
102566845  SPHK2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
102562157  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102574430  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102575936  GTPase HRas [KO:K07827]
102566357  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102576986  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102563228  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
106736997  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
106737342  mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102561718  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109282845  mitogen-activated protein kinase 3-like [KO:K04371] [EC:2.7.11.24]
102571708  cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
102572619  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
102571930  cytosolic phospholipase A2 epsilon-like [KO:K16342] [EC:3.1.1.4]
102571167  cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
106736657  cytosolic phospholipase A2 zeta-like [KO:K16342] [EC:3.1.1.4]
102572385  cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
102573324  PLA2G4F; cytosolic phospholipase A2 delta [KO:K16342] [EC:3.1.1.4]
102568256  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
102572848  PLA2G4D; phospholipase A2 group IVD [KO:K16342] [EC:3.1.1.4]
102573092  cytosolic phospholipase A2 zeta-like [KO:K16342] [EC:3.1.1.4]
102568705  PLA2G4F.1; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
102570036  PLA2G4C; phospholipase A2 group IVC [KO:K16342] [EC:3.1.1.4]
102564564  PLA2G4A; phospholipase A2 group IVA [KO:K16342] [EC:3.1.1.4]
102576759  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
102576061  PPP3CC; protein phosphatase 3 catalytic subunit gamma [KO:K04348] [EC:3.1.3.16]
102573328  PPP3CB; protein phosphatase 3 catalytic subunit beta [KO:K04348] [EC:3.1.3.16]
106737480  PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268]
102565601  NFATC2; nuclear factor of activated T-cells 2 [KO:K17332]
106736995  PTGS2; prostaglandin-endoperoxide synthase 2 [KO:K11987] [EC:1.14.99.1]
106736955  PTK2; protein tyrosine kinase 2 [KO:K05725] [EC:2.7.10.2]
102565747  SHC2; SHC adaptor protein 2 [KO:K17447]
102559351  PXN; paxillin [KO:K05760]
102558748  CDC42; cell division cycle 42 [KO:K04393]
102571419  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102571177  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
106736779  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102565670  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102563674  MAPKAPK2; mitogen-activated protein kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
106736633  MAPKAPK3; mitogen-activated protein kinase-activated protein kinase 3 [KO:K04444] [EC:2.7.11.1]
102575596  HSPB1; heat shock protein family B (small) member 1 [KO:K04455]
102567804  SRC; SRC proto-oncogene, non-receptor tyrosine kinase [KO:K05704] [EC:2.7.10.2]
102564312  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
106737094  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
102571877  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
106737141  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102567863  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102570922  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102576455  RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
102567702  RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
102563759  RAC3; ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [KO:K07861]
102574794  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102558879  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102564996  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
102575253  NOS3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
102573968  CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
109282419  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
Related
pathway
amj00590  Arachidonic acid metabolism
amj04010  MAPK signaling pathway
amj04020  Calcium signaling pathway
amj04510  Focal adhesion
KO pathway
ko04370   
LinkDB

DBGET integrated database retrieval system