βII Protein kinase c is required for the G2/M phase transition of cell cycle

Larry J. Thompson, Alan P Fields

Research output: Contribution to journalArticle

Abstract

Entry into mitosis requires the coordinated action of multiple mitotic protein kinases. Treatment of synchronized HL60 cells with the highly selective PKC inhibitor chelerythrine chloride leads to profound cell cycle arrest in G2 phase. The cellular effects of chelerythrine are not due either direct or indirect inhibition of the known mitotic regulator, cdc2/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 βu 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 phosphorvlation of nuclear lamin B is important in these events.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - 1996
Externally publishedYes

Fingerprint

G2 Phase
Phase Transition
phase transition
interphase
protein kinases
Cell Division
mitosis
Protein Kinases
cell cycle
Cell Cycle
Phase transitions
Cells
Lamin Type B
Nuclear Lamina
Mitosis
Chemical activation
degradation
Cyclin B
Degradation
cyclins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

βII Protein kinase c is required for the G2/M phase transition of cell cycle. / Thompson, Larry J.; Fields, Alan P.

In: FASEB Journal, Vol. 10, No. 6, 1996.

Research output: Contribution to journalArticle

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AB - Entry into mitosis requires the coordinated action of multiple mitotic protein kinases. Treatment of synchronized HL60 cells with the highly selective PKC inhibitor chelerythrine chloride leads to profound cell cycle arrest in G2 phase. The cellular effects of chelerythrine are not due either direct or indirect inhibition of the known mitotic regulator, cdc2/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 βu 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 phosphorvlation of nuclear lamin B is important in these events.

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