Protein kinase D regulates cofilin activity through p21-activated kinase 4

Samantha J. Spratley, Ligia I. Bastea, Heike Döppler, Kensaku Mizuno, Peter Storz

    Research output: Contribution to journalArticlepeer-review

    54 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)34254-34261
    Number of pages8
    JournalJournal of Biological Chemistry
    Volume286
    Issue number39
    DOIs
    Publication statusPublished - 2011 Oct 30

    ASJC Scopus subject areas

    • Biochemistry
    • Molecular Biology
    • Cell Biology

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