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VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in tumor angiogenesis.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Genetics and Pathology.
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2005 (English)In: EMBO J, ISSN 0261-4189, Vol. 24, no 13, 2342-53 p.Article in journal (Refereed) Published
Abstract [en]

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.
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URN: urn:nbn:se:uu:diva-74136PubMedID: 15962004OAI: oai:DiVA.org:uu-74136DiVA: diva2:102046
Available from: 2005-08-31 Created: 2005-08-31 Last updated: 2011-01-11

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Bohman, SvanteDixelius, JohanDimberg, AnnaMagnusson, PeetraWikner, CharlotteWernstedt, ChristerClaesson-Welsh, Lena

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