βIIprotein kinase C is required for the G2/M phase transition of cell cycle

Larry J. Thompson, Alan P. Fields

Research output: Contribution to journalArticle

127 Scopus citations

Abstract

Entry into mitosis requires the coordinated action of multiple mitotic protein kinases. In this report, we investigate the involvement of protein kinase C in the control of mitosis in human cells. Treatment of synchronized HL60 cells with the highly selective protein kinase C (PKC) inhibitor chelerythrine chloride leads to profound cell cycle arrest in G2 phase. The cellular effects of chelerythrine are not due to either direct or indirect inhibition of the known mitotic regulator p34cdc2/cyclin B kinase. Rather, several lines of evidence demonstrate that chelerythrine-mediated G2 phase arrest results from selective inhibition and degradation of βII protein kinase C. First, chelerythrine causes dose-dependent inhibition of βII PKC in vitro with an IC50 identical to that for G2 phase blockade in whole cells. Second, chelerythrine specifically inhibits βII PKC-mediated lamin B phosphorylation and mitotic nuclear lamina disassembly. Third, chelerythrine leads to selective loss of βII PKC during G2 phase in synchronized cells. Fourth, chelerythrine mediates activation-dependent degradation of PKC, indicating that βII PKC is selectively activated during G2 phase of cell cycle. Taken together, these data demonstrate that βII PKC activation at G2 phase is required for mitotic nuclear lamina disassembly and entry into mitosis and that βII PKC-mediated phosphorylation of nuclear lamin B is important in these events.

Original languageEnglish (US)
Pages (from-to)15045-15053
Number of pages9
JournalJournal of Biological Chemistry
Volume271
Issue number25
DOIs
StatePublished - Jan 1 1996

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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