VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis.
2005 (English)In: EMBO J, ISSN 0261-4189, Vol. 24, no 13, 2342-53 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2005. Vol. 24, no 13, 2342-53 p.
IdentifiersURN: urn:nbn:se:uu:diva-74136PubMedID: 15962004OAI: oai:DiVA.org:uu-74136DiVA: diva2:102046