Protein Kinase D Regulates Cofilin Activity Through P21-activated Kinase 4

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2011 Aug 12

PMID 21832093

Citations 45

Authors

Samantha J Spratley

Ligia I Bastea

Heike Doppler

Kensaku Mizuno

Peter Storz

Affiliations

Soon will be listed here.

Abstract

Dynamic reorganization of the actin cytoskeleton at the leading edge is required for directed cell migration. Cofilin, a small actin-binding protein with F-actin severing activities, is a key enzyme initiating such actin remodeling processes. Cofilin activity is tightly regulated by phosphorylation and dephosphorylation events that are mediated by LIM kinase (LIMK) and the phosphatase slingshot (SSH), respectively. Protein kinase D (PKD) is a serine/threonine kinase that inhibits actin-driven directed cell migration by phosphorylation and inactivation of SSH. Here, we show that PKD can also regulate LIMK through direct phosphorylation and activation of its upstream kinase p21-activated kinase 4 (PAK4). Therefore, active PKD increases the net amount of phosphorylated inactive cofilin in cells through both pathways. The regulation of cofilin activity at multiple levels may explain the inhibitory effects of PKD on barbed end formation as well as on directed cell migration.

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