TY - JOUR
T1 - Phosphorylation of the Par-1 polarity kinase by protein kinase D regulates 14-3-3 binding and membrane association
AU - Watkins, Janis L.
AU - Lewandowski, Katherine T.
AU - Meek, Sarah E.M.
AU - Storz, Peter
AU - Toker, Alex
AU - Piwnica-Worms, Helen
PY - 2008/11/25
Y1 - 2008/11/25
N2 - 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.
AB - 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.
KW - Atypical protein kinase C
KW - Cell polarity
KW - EMK
KW - MARK2
UR - http://www.scopus.com/inward/record.url?scp=57449086843&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=57449086843&partnerID=8YFLogxK
U2 - 10.1073/pnas.0809661105
DO - 10.1073/pnas.0809661105
M3 - Article
C2 - 19011111
AN - SCOPUS:57449086843
SN - 0027-8424
VL - 105
SP - 18378
EP - 18383
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 47
ER -