VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis. EMBO J 2005 Jul 06;24(13):2342-53
Date
06/18/2005Pubmed ID
15962004Pubmed Central ID
PMC1173150DOI
10.1038/sj.emboj.7600709Scopus ID
2-s2.0-22744447871 (requires institutional sign-in at Scopus site) 230 CitationsAbstract
Vascular endothelial growth factor receptor-2 (VEGFR-2) activation by VEGF-A is essential in vasculogenesis and angiogenesis. We have generated a pan-phosphorylation site map of VEGFR-2 and identified one major tyrosine phosphorylation site in the kinase insert (Y951), in addition to two major sites in the C-terminal tail (Y1175 and Y1214). In developing vessels, phosphorylation of Y1175 and Y1214 was detected in all VEGFR-2-expressing endothelial cells, whereas phosphorylation of Y951 was identified in a subset of vessels. Phosphorylated Y951 bound the T-cell-specific adapter (TSAd), which was expressed in tumor vessels. Mutation of Y951 to F and introduction of phosphorylated Y951 peptide or TSAd siRNA into endothelial cells blocked VEGF-A-induced actin stress fibers and migration, but not mitogenesis. Tumor vascularization and growth was reduced in TSAd-deficient mice, indicating a critical role of Y951-TSAd signaling in pathological angiogenesis.
Author List
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 LMESH terms used to index this publication - Major topics in bold
ActinsAdaptor Proteins, Signal Transducing
Amino Acid Sequence
Animals
Binding Sites
Cell Line, Tumor
Cells, Cultured
Endothelial Cells
Fibrosarcoma
Humans
Kidney Neoplasms
Mice
Molecular Sequence Data
Neovascularization, Pathologic
Phosphorylation
RNA, Small Interfering
Signal Transduction
Stem Cells
Tyrosine
Vascular Endothelial Growth Factor Receptor-2