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

FEBS Letters

Zeiher, Andreas M¹  Dimmeler, Stefanie¹  Dernbach, Elisabeth¹ 

[1] Molecular Cardiology, Department of Internal Medicine IV, University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany

关键词: Migration;    Proliferation;    Protein kinase;    Nitric oxide;    Vascular endothelial growth factor;   

DOI  :  10.1016/S0014-5793(00)01657-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 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.

【 授权许可】

Unknown