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J Biol Chem, Vol. 273, Issue 19, 11514-11520, May 8, 1998

Phosphatidylglycerol Is a Physiologic Activator of Nuclear Protein Kinase C

Nicole R. MurrayDagger § and Alan P. FieldsDagger §

From the Dagger  Sealy Center for Oncology and Hematology and the Departments of § Human Biological Chemistry and Genetics and  Pharmacology, University of Texas Medical Branch, Galveston, Texas 77555-1048

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 beta 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 beta 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 beta 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 beta 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 beta II, the same region we previously implicated in NMAF-mediated activation of PKC beta II. Taken together, our results indicate that specific molecular species of nuclear PG function to physiologically regulate PKC beta II activity at the nucleus.


Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.



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