Phosphorylation of the Par-1 polarity kinase by protein kinase D regulates 14-3-3 binding and membrane association

Janis L. Watkins, Katherine T. Lewandowski, Sarah E.M. Meek, Peter Storz, Alex Toker, Helen Piwnica-Worms

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


The Par-1 protein kinases are conserved from yeast to humans, where they function as key polarity determinants. The mammalian Par-1 family is comprised of 4 members (Par-1a, -b, -c, and -d). Previously, we demonstrated that atypical protein kinase C (aPKC) phosphorylates the Par-1 kinases on a conserved threonine residue (T595) to regulate localization and kinase activity. Here, we demonstrate that Par-1b is also regulated by another arm of the PKC pathway, one that involves novel PKCs (nPKC) and protein kinase D. Treatment of cells with the PKC activator phorbol-12-myristate-13-acetate (PMA) potently stimulated phosphorylation of Par-1b on serine 400 (S400), a residue that is conserved in all 4 mammalian Par-1 kinases as well as the fly ortholog. We demonstrate that PMA stimulates nPKC to activate PKD, which in turn directly phosphorylates Par-1b on S400 to positively regulate 14-3-3 binding and to negatively regulate membrane association. Thus, 2 arms of the PKC pathway regulate interactions between Par-1b and 14-3-3 proteins: one involving aPKC and the other nPKC/PKD.

Original languageEnglish (US)
Pages (from-to)18378-18383
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number47
StatePublished - Nov 25 2008


  • Atypical protein kinase C
  • Cell polarity
  • EMK
  • MARK2

ASJC Scopus subject areas

  • General


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