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 journalArticle

49 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 (US)
Pages (from-to)34254-34261
Number of pages8
JournalJournal of Biological Chemistry
Volume286
Issue number39
DOIs
StatePublished - Oct 30 2011

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p21-Activated Kinases
Actin Depolymerizing Factors
Phosphorylation
Actins
Lim Kinases
Cell Movement
Microfilament Proteins
Protein-Serine-Threonine Kinases
Actin Cytoskeleton
Phosphoric Monoester Hydrolases
Phosphotransferases
Chemical activation
protein kinase D
Enzymes

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Protein kinase D regulates cofilin activity through p21-activated kinase 4. / Spratley, Samantha J.; Bastea, Ligia I.; Döppler, Heike; Mizuno, Kensaku; Storz, Peter.

In: Journal of Biological Chemistry, Vol. 286, No. 39, 30.10.2011, p. 34254-34261.

Research output: Contribution to journalArticle

Spratley, Samantha J. ; Bastea, Ligia I. ; Döppler, Heike ; Mizuno, Kensaku ; Storz, Peter. / Protein kinase D regulates cofilin activity through p21-activated kinase 4. In: Journal of Biological Chemistry. 2011 ; Vol. 286, No. 39. pp. 34254-34261.
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