Mapping of a molecular determinant for protein kinase C β(II) isozyme function

Yesim Gökmen-Polar, Alan P. Fields

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

In human erythroleukemia (K562) cells, the highly related protein kinase C (PKC) α and PKC β(II) isozymes serve distinct functions in cellular differentiation and proliferation, respectively. Previous studies using two domain switch PKC chimera revealed that the Catalytic domains of PKC α and β(II) contain molecular determinants important for isozyme-specific function (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 have now analyzed a panel of PKC chimeras to determine the specific region within the catalytic domain important for PKC β(II) function. A cellular assay for PKC β(II) function was devised based on the finding that PKC β(II) selectively translocates to the nucleus and phosphorylates nuclear lamin B in response to the PKC activator bryostatin. This response is strictly dependent upon expression of PKC β(II) or a PKC chimera that functions like PKC β(II). We demonstrate that a PKC α/β(II) chimera containing only the carboxyl-terminal 13 amino acids from PKC β(II) (β(II) V5) is capable of nuclear translocation and lamin B phosphorylation. These results are consistent with our recent observation that the PKC β(II) V5 region binds to phosphatidylglycerol (PG), a potent and selective PKC β(II) activator present in the nuclear membrane (Murray, N. R., and Fields, A. P. (1998) J. Biol. Chem. 273, 11514-11520). Soluble β(II) V5 peptide selectively inhibits PG-stimulated PKC β(II) activity in a dose-dependent fashion, indicating that PG-mediated activation of PKC β(II) involves interactions with the β(II) V5 region of the enzyme. We conclude that β(II) V5 is a major determinant for PKC β(II) nuclear function and suggest a model in which binding of PG to the β(II) V5 region stimulates nuclear PKC β(II) activity during G2 phase of the cell cycle.

Original languageEnglish (US)
Pages (from-to)20261-20266
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number32
DOIs
StatePublished - Aug 7 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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