14-3-3epsilon inhibits MK5-mediated cell migration by disrupting F-actin polymerization

Abstract

The signal pathway by which 14-3-3 epsilon inhibits cell migration induced by MAPK-activated protein kinase 5 (MK5) was investigated in cultured HeLa cells. Both in vivo and in vitro analyses have revealed that 14-3-3e interacts with MK5. 14-3-3e bound to MK5 inhibits the pbosphorylation of HSP27, a known substrate of MK5. Disturbance of actin cytoskeleton organization by 14-3-3 epsilon was shown in transfected cells transiently expressing 14-3-3 epsilon as well as established cells stably expressing 14-3-3e. Moreover, overexpression of 14-3-3e resulted in the inhibition of cell migration induced by MK5 overexpression or TNF alpha treatment. Our results suggest that 14-3-3 epsilon bound to MK5 inhibits cell migration by inhibiting the phosphorylation of HSP27 whose phospborylation regulates F-actin polymerization, actin cytoskeleton organization and subsequent actinfilament dynamics. (C) 2007 Elsevier Inc. All rights reserved.