Protein kinase D-mediated phosphorylation at Ser99 regulates localization of p21-activated kinase 4

Ligia I. Bastea, Heike Döppler, Sarah E. Pearce, Nisha Durand, Samantha J. Spratley, Peter Storz

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

PAKs (p21-activated kinases) are effectors of RhoGTPases. PAK4 contributes to regulation of cofilin at the leading edge of migrating cells through activation of LIMK (Lin-11/Isl-1/Mec-3 kinase). PAK4 activity is regulated by an autoinhibitory domain that is released upon RhoGTPase binding as well as phosphorylation at Ser474 in the activation loop of the kinase domain. In the present study, we add another level of complexity to PAK4 regulation by showing that phosphorylation at Ser99 is required for its targeting to the leading edge. This phosphorylation is mediated by PKD1 (protein kinase D1). Phosphorylation of PAK4 at Ser99 also mediates binding to 14-3-3 protein, and is required for the formation of a PAK4-LIMK-PKD1 complex that regulates cofilin activity and directed cell migration.

Original languageEnglish (US)
Pages (from-to)251-260
Number of pages10
JournalBiochemical Journal
Volume455
Issue number2
DOIs
StatePublished - Oct 15 2013

Keywords

  • 14-3-3 protein
  • Leading edge
  • Localization
  • P21-activated kinase 4 (PAK4)
  • Protein kinase D (PKD)
  • RhoGTPase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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