KEGG   PATHWAY: ko04370
ko04370                     Pathway                                
VEGF signaling pathway
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
ko04370  VEGF signaling pathway

Other DBs
GO: 0048010
K05448  vascular endothelial growth factor A
K05098  kinase insert domain protein receptor [EC:]
K08273  SH2 domain-containing protein 2A
K01116  phosphatidylinositol phospholipase C, gamma-1 [EC:]
K05859  phosphatidylinositol phospholipase C, gamma-2 [EC:]
K02677  classical protein kinase C alpha type [EC:]
K19662  classical protein kinase C beta type [EC:]
K19663  classical protein kinase C gamma type [EC:]
K04718  sphingosine kinase [EC:]
K02833  GTPase HRas
K07827  GTPase KRas
K07828  GTPase NRas
K04366  RAF proto-oncogene serine/threonine-protein kinase [EC:]
K04368  mitogen-activated protein kinase kinase 1 [EC:]
K04369  mitogen-activated protein kinase kinase 2 [EC:]
K04371  mitogen-activated protein kinase 1/3 [EC:]
K16342  cytosolic phospholipase A2 [EC:]
K04348  serine/threonine-protein phosphatase 2B catalytic subunit [EC:]
K06268  serine/threonine-protein phosphatase 2B regulatory subunit
K17332  nuclear factor of activated T-cells, cytoplasmic 2
K11987  prostaglandin-endoperoxide synthase 2 [EC:]
K05725  focal adhesion kinase 1 [EC:]
K17447  SHC-transforming protein 2
K05760  paxillin
K04393  cell division control protein 42
K04441  p38 MAP kinase [EC:]
K04443  mitogen-activated protein kinase-activated protein kinase 2 [EC:]
K04444  mitogen-activated protein kinase-activated protein kinase 3 [EC:]
K04455  heat shock protein beta-1
K05704  tyrosine-protein kinase Src [EC:]
K00922  phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:]
K02649  phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04392  Ras-related C3 botulinum toxin substrate 1
K07860  Ras-related C3 botulinum toxin substrate 2
K07861  Ras-related C3 botulinum toxin substrate 3
K04456  RAC serine/threonine-protein kinase [EC:]
K13242  nitric-oxide synthase, endothelial [EC:]
K04399  caspase 9 [EC:]
K02158  Bcl-2-antagonist of cell death
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)
ko00590  Arachidonic acid metabolism
ko04010  MAPK signaling pathway
ko04020  Calcium signaling pathway
ko04151  PI3K-Akt signaling pathway
ko04510  Focal adhesion

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