TI - MAPKAPK-2 -mediated LIM-kinase activation is critical for VEGF -induced actin remodeling and cell migration . AB - Vascular endothelial growth factor-A ( VEGF-A ) induces actin reorganization and migration of endothelial cells through a p38 mitogen-activated protein kinase ( MAPK ) pathway . LIM-kinase 1 ( LIMK1 ) induces actin remodeling by phosphorylating and inactivating cofilin , an actin-depolymerizing factor . In this study , we demonstrate that activation of LIMK1 by MAPKAPK-2 ( MK2 ; a downstream kinase of p38 MAPK ) represents a novel signaling pathway in VEGF-A -induced cell migration . VEGF-A induced LIMK1 activation and cofilin phosphorylation , and this was inhibited by the p38 MAPK inhibitor SB203580 . Although p38 phosphorylated LIMK1 at Ser-310 , it failed to activate LIMK1 directly ; however , MK2 activated LIMK1 by phosphorylation at Ser-323 . Expression of a Ser-323-non-phosphorylatable mutant of LIMK1 suppressed VEGF-A -induced stress fiber formation and cell migration ; however , expression of a Ser-323-phosphorylation-mimic mutant enhanced these processes . Knockdown of MK2 by siRNA suppressed VEGF-A -induced LIMK1 activation , stress fiber formation , and cell migration . Expression of kinase -dead LIMK1 suppressed VEGF-A -induced tubule formation . These findings suggest that MK2 -mediated LIMK1 phosphorylation/activation plays an essential role in VEGF-A -induced actin reorganization , migration , and tubule formation of endothelial cells .