Phosphorylation of the endothelial nitric oxide synthase at ser‐1177 is required for VEGF‐induced endothelial cell migration
S Dimmeler, E Dernbach, AM Zeiher - FEBS letters, 2000 - Wiley Online Library
S Dimmeler, E Dernbach, AM Zeiher
FEBS letters, 2000•Wiley Online LibraryVascular 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 …
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 …
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.
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