Phosphorylation of the endothelial nitric oxide synthase at Ser-1177 is required for VEGF-induced endothelial cell migration

被引：320

作者：

Dimmeler, S ^{[1
]}

Dernbach, E ^{[1
]}

Zeiher, AM ^{[1
]}

机构：

[1] Goethe Univ Frankfurt, Dept Internal Med 4, D-60590 Frankfurt, Germany

来源：

FEBS LETTERS | 2000年 / 477卷 / 03期

关键词：

migration; proliferation; protein kinase; nitric oxide; vascular endothelial growth factor;

D O I：

10.1016/S0014-5793(00)01657-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Vascular endothelial growth factor (VEGF) stimulates endothelial cell (EC) migration. The protein kinase Akt activates the endothelial NO synthase (eNOS) by phosphorylation of Ser-1177, Therefore, we investigated the contribution of Akt-mediated eNOS phosphorylation to VEGF-induced EC migration. Inhibition of NO synthase or overexpression of a dominant negative Akt abrogated VEGF-induced cell migration. In contrast, overexpression of constitutively active Akt was sufficient to induce cell migration. Moreover, transfection of an Akt site phospho-mimetic eNOS (S1177D) potently stimulated EC migration, whereas a non-phosphorylatable mutant (S1177A) inhibited VEGF-induced EC migration. Our data indicate that eNOS activation via phosphorylation of Ser-1177 by Akt is necessary and sufficient for VEGF-mediated EC migration. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V, All rights reserved.

引用

页码：258 / 262

页数：5

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