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

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.
Mesh Terms:
14-3-3 Proteins, Cell Line, Cell Membrane, Cell Polarity, Enzyme Activation, Humans, Mutagenesis, Site-Directed, Phosphorylation, Protein Binding, Protein Kinase C, Protein-Serine-Threonine Kinases, Tetradecanoylphorbol Acetate
Proc. Natl. Acad. Sci. U.S.A.
Date: Nov. 25, 2008
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