KEGG   PATHWAY: rno04370
rno04370                    Pathway                                

VEGF signaling pathway - Rattus norvegicus (rat)
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.
Environmental Information Processing; Signal transduction
Pathway map
rno04370  VEGF signaling pathway

Other DBs
GO: 0048010
Rattus norvegicus (rat) [GN:rno]
83785  Vegfa; vascular endothelial growth factor A isoform 6 precursor [KO:K05448]
25589  Kdr; vascular endothelial growth factor receptor 2 precursor [KO:K05098] [EC:]
310688  Sh2d2a; SH2 domain-containing protein 2A [KO:K08273]
25738  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:]
29337  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:]
24680  Prkca; protein kinase C alpha type [KO:K02677] [EC:]
25023  Prkcb; protein kinase C beta type isoform 2 [KO:K19662] [EC:]
24681  Prkcg; protein kinase C gamma type [KO:K19663] [EC:]
308589  Sphk2; sphingosine kinase 2 [KO:K04718] [EC:]
170897  Sphk1; sphingosine kinase 1 isoform b [KO:K04718] [EC:]
293621  Hras; GTPase HRas [KO:K02833]
367858  GTPase HRas [KO:K02833]
24525  Kras; GTPase KRas [KO:K07827]
24605  Nras; GTPase NRas [KO:K07828]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:]
58960  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:]
296091  Pla2g4e; cytosolic phospholipase A2 epsilon isoform X1 [KO:K16342] [EC:]
24653  Pla2g4a; cytosolic phospholipase A2 [KO:K16342] [EC:]
311341  Pla2g4b; cytosolic phospholipase A2 beta [KO:K16342] [EC:]
691905  Pla2g4d; cytosolic phospholipase A2 delta [KO:K16342] [EC:]
691907  Pla2g4f; cytosolic phospholipase A2 zeta [KO:K16342] [EC:]
691810  Pla2g4c; phospholipase A2, group IVC [KO:K16342] [EC:]
24674  Ppp3ca; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:]
24675  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:]
171378  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:]
29748  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
29749  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
311658  Nfatc2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
29527  Ptgs2; prostaglandin G/H synthase 2 precursor [KO:K11987] [EC:]
25614  Ptk2; focal adhesion kinase 1 [KO:K05725] [EC:]
314612  Shc2; SHC-transforming protein 2 [KO:K17447]
360820  Pxn; paxillin [KO:K05760]
64465  Cdc42; cell division control protein 42 homolog [KO:K04393]
81649  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:]
60352  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:]
29513  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:]
689314  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:]
289014  Mapkapk2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:]
315994  Mapkapk3; MAP kinase-activated protein kinase 3 [KO:K04444] [EC:]
24471  Hspb1; heat shock protein beta-1 [KO:K04455]
83805  Src; proto-oncogene tyrosine-protein kinase Src [KO:K05704] [EC:]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
363875  Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
366957  Rac2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:]
24600  Nos3; nitric oxide synthase, endothelial [KO:K13242] [EC:]
58918  Casp9; caspase-9 [KO:K04399] [EC:]
64639  Bad; bcl2-associated agonist of cell death [KO:K02158]
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
Cross MJ, Dixelius J, Matsumoto T, Claesson-Welsh L.
VEGF-receptor signal transduction.
Trends Biochem Sci 28:488-94 (2003)
Matsumoto T, Claesson-Welsh L.
VEGF receptor signal transduction.
Sci STKE 2001:RE21 (2001)
Hoeben A, Landuyt B, Highley MS, Wildiers H, Van Oosterom AT, De Bruijn EA.
Vascular endothelial growth factor and angiogenesis.
Pharmacol Rev 56:549-80 (2004)
Takahashi H, Shibuya M.
The vascular endothelial growth factor (VEGF)/VEGF receptor system and its role under physiological and pathological conditions.
Clin Sci (Lond) 109:227-41 (2005)
Zachary I.
VEGF signalling: integration and multi-tasking in endothelial cell biology.
Biochem Soc Trans 31:1171-7 (2003)
Munoz-Chapuli R, Quesada AR, Angel Medina M.
Angiogenesis and signal transduction in endothelial cells.
Cell Mol Life Sci 61:2224-43 (2004)
Lamalice L, Houle F, Jourdan G, Huot J.
Phosphorylation of tyrosine 1214 on VEGFR2 is required for VEGF-induced activation of Cdc42 upstream of SAPK2/p38.
Oncogene 23:434-45 (2004)
Shu X, Wu W, Mosteller RD, Broek D.
Sphingosine kinase mediates vascular endothelial growth factor-induced activation of ras and mitogen-activated protein kinases.
Mol Cell Biol 22:7758-68 (2002)
rno00590  Arachidonic acid metabolism
rno04010  MAPK signaling pathway
rno04020  Calcium signaling pathway
rno04151  PI3K-Akt signaling pathway
rno04510  Focal adhesion
KO pathway

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