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Journal Articles Circulation Research Year : 2005

Vascular endothelial-cadherin tyrosine phosphorylation in angiogenic and quiescent adult tissues.

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Abstract

Vascular endothelial-cadherin (VE-cadherin) plays a key role in angiogenesis and in vascular permeability. The regulation of its biological activity may be a central mechanism in normal or pathological angiogenesis. VE-cadherin has been shown to be phosphorylated on tyrosine in vitro under various conditions, including stimulation by VEGF. In the present study, we addressed the question of the existence of a tyrosine phosphorylated form of VE-cadherin in vivo, in correlation with the quiescent versus angiogenic state of adult tissues. Phosphorylated VE-cadherin was detected in mouse lung, uterus, and ovary but not in other tissues unless mice were injected with peroxovanadate to block protein phosphatases. Remarkably, VE-cadherin tyrosine phosphorylation was dramatically increased in uterus and ovary, and not in other organs, during PMSG/hCG-induced angiogenesis. In parallel, we observed an increased association of VE-cadherin with Flk1 (VEGF receptor 2) during hormonal angiogenesis. Additionally, Src kinase was constitutively associated with VE-cadherin in both quiescent and angiogenic tissues and increased phosphorylation of VE-cadherin-associated Src was detected in uterus and ovary after hormonal treatment. Src-VE-cadherin association was detected in cultured endothelial cells, independent of VE-cadherin phosphorylation state and Src activation level. In this model, Src inhibition impaired VEGF-induced VE-cadherin phosphorylation, indicating that VE-cadherin phosphorylation was dependent on Src activation. We conclude that VE-cadherin is a substrate for tyrosine kinases in vivo and that its phosphorylation, together with that of associated Src, is increased by angiogenic stimulation. Physical association between Flk1, Src, and VE-cadherin may thus provide an efficient mechanism for amplification and perpetuation of VEGF-stimulated angiogenic processes.
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Origin : Files produced by the author(s)
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Origin : Files produced by the author(s)
Origin : Files produced by the author(s)

Dates and versions

inserm-00433466 , version 1 (19-11-2009)

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Nathalie Lambeng, Yann Wallez, Christine Rampon, Francine Cand, Georges Christé, et al.. Vascular endothelial-cadherin tyrosine phosphorylation in angiogenic and quiescent adult tissues.: VE-cadherin tyrosine phosphorylation. Circulation Research, 2005, 96 (3), pp.384-91. ⟨10.1161/01.RES.0000156652.99586.9f⟩. ⟨inserm-00433466⟩
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