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

FEBS Lett. 2000 Jul 21;477(3):258-62. doi: 10.1016/s0014-5793(00)01657-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Endothelial Growth Factors / pharmacology*
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / enzymology
  • Humans
  • Lymphokines / pharmacology*
  • Nitric Oxide Synthase / chemistry
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type III
  • Phosphorylation
  • Serine / metabolism*
  • Transfection
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors

Substances

  • Endothelial Growth Factors
  • Lymphokines
  • Vascular Endothelial Growth Factor A
  • Vascular Endothelial Growth Factors
  • Serine
  • NOS3 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type III