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Phosphorylation of the endothelial nitric oxide synthase at Ser‐1177 is required for VEGF‐induced endothelial cell migration
Author(s) -
Dimmeler Stefanie,
Dernbach Elisabeth,
Zeiher Andreas M
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01657-4
Subject(s) - protein kinase b , enos , phosphorylation , cell migration , microbiology and biotechnology , chemistry , nitric oxide synthase type iii , endothelial stem cell , nitric oxide synthase , cell , biology , biochemistry , in vitro , enzyme
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.