VEGFR2 autophosphorylates

Stable Identifier
R-HSA-4420117
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Binding of VEGFA to VEGFR2 induces receptor dimerization and autophosphorylation, leading to the recruitment of downstream signalling molecules. Once the two VEGFR2 receptors are cross-linked to each other, via simultaneous interaction with VEGFA dimer, their membrane-proximal Ig-like domain 7s are held in close proximity so that low-affinity homotypic interactions between these domains further stabilise the receptor dimers. This allows for the exact positioning of the intracellular kinase domains resulting in VEGFR2 autophosphorylation (Ruch et al. 2007, Holmes at al. 2007). The major tyrosine residues known to be autophosphorylated are Y801 and Y951 in the kinase-insert domain, Y1054 and Y1059 within the kinase domain, and Y1175 and Y1214 in the C-terminal tail of VEGFR (Dougher-Vermazen et al. 1994, Cunningham et al. 2007, Kendall et al. 1999, Matsumoto et al. 2005). The Y1175 (mice Y1173) is crucial for endothelial and haemopoietic cell development. Mice with muatation Y1173F die between E8.5 and E9.5 from lack of endothelial and haemopoietic development (Sakurai et al. 2005).

Literature References
PubMed ID Title Journal Year
15962004 VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis

Matsumoto, T, Bohman, S, Dixelius, J, Berge, T, Dimberg, A, Magnusson, P, Wang, L, Wikner, C, Qi, JH, Wernstedt, C, Wu, J, Bruheim, S, Mugishima, H, Mukhopadhyay, D, Spurkland, A, Claesson-Welsh, L

EMBO J. 2005
10037737 Vascular endothelial growth factor receptor KDR tyrosine kinase activity is increased by autophosphorylation of two activation loop tyrosine residues

Kendall, RL, Rutledge, RZ, Mao, X, Tebben, AJ, Hungate, RW, Thomas, KA

J. Biol. Chem. 1999
9398617 Interactions of FLT-1 and KDR with phospholipase C gamma: identification of the phosphotyrosine binding sites

Cunningham, SA, Arrate, MP, Brock, TA, Waxham, MN

Biochem. Biophys. Res. Commun. 1997
Participants
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Catalyst Activity
Catalyst Activity
Title
protein tyrosine kinase activity of VEGFA-165 dimer:VEGFR2 dimer [plasma membrane]
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Activity
Orthologous Events
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