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

Watkins, J. L., Lewandowski, K. T., Meek, S. E.M., Storz, P., Toker, A. and Piwnica-Worms, H. (2008) Phosphorylation of the Par-1 polarity kinase by protein kinase D regulates 14-3-3 binding and membrane association. Proceedings of the National Academy of Sciences of the United States of America, 105(47), pp. 18378-18383. (doi: 10.1073/pnas.0809661105)

Abstract

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Meek, Dr Sarah
• Authors: Watkins, J. L., Lewandowski, K. T., Meek, S. E.M., Storz, P., Toker, A., and Piwnica-Worms, H.
• College/School: College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Proceedings of the National Academy of Sciences of the United States of America
• Journal Abbr.: PNAS
• Publisher: National Academy of Sciences
• ISSN: 0027-8424
• ISSN (Online): 1091-6490