Phosphatidylglycerol is a physiologic activator of nuclear protein kinase C

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

A major mechanism by which protein kinase C (PKC) function is regulated is through the selective targeting and activation of individual PKC isotypes at distinct subcellular locations. PKC β(II) is selectively activated at the nucleus during G2 phase of cell cycle where it is required for entry into mitosis. Selective nuclear activation of PKC β(II) is conferred by molecular determinants within the carboxyl-terminal catalytic domain of the kinase (Walker, S. D., Murray, N. R., Burns, D. J., and Fields, A. P. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 9156-9160). We previously described a lipid-like PKC activator in nuclear membranes, termed nuclear membrane activation factor (NMAF), that potently stimulates PKC β(II) activity through interactions involving this domain (Murray, N. R., Burns, D. J., and Fields, A. P. (1994) J. Biol. Chem. 269, 21385-21390). We have now identified NMAF as phosphatidylglycerol (PG), based on several lines of evidence. First, NMAF cofractionates with PG as a single peak of activity through multiple chromatographic separations and exhibits phospholipase sensitivity identical to that of PG. Second, purified PG, but not other phospholipids, exhibits dose-dependent NMAF activity. Third, defined molecular species of PG exhibit different abilities to stimulate PKC β(II) activity. 1,2-Dioleoyl-PG possesses significantly higher activity than other PG species, suggesting that both fatty acid side chain composition and the glycerol head group are important determinants for activity. Fourth, in vitro binding studies demonstrate that PG binds to the carboxyl-terminal region of PKC β(II), the same region we previously implicated in NMAF-mediated activation of PKC β(II). Taken together, our results indicate that specific molecular species of nuclear PG function to physiologically regulate PKC β(II) activity at the nucleus.

Original languageEnglish (US)
Pages (from-to)11514-11520
Number of pages7
JournalJournal of Biological Chemistry
Volume273
Issue number19
DOIs
StatePublished - May 8 1998
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry

Cite this