betaII protein kinase C is required for the G2/M phase transition of cell cycle.
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 p34(cdc2)/cyclin B kinase. Rather, several lines of evidence demonstrate that chelerythrine-mediated G2 phase arrest results from selective inhibition and degradation of betaII protein kinase C. First, chelerythrine causes dose-dependent inhibition of betaII PKC in vitro with an IC50 identical to that for G2 phase blockade in whole cells. Second, chelerythrine specifically inhibits betaII PKC-mediated lamin B phosphorylation and mitotic nuclear lamina disassembly. Third, chelerythrine leads to selective loss of betaII PKC during G2 phase in synchronized cells. Fourth, chelerythrine mediates activation-dependent degradation of PKC, indicating that betaII PKC is selectively activated during G2 phase of cell cycle. Taken together, these data demonstrate that betaII PKC activation at G2 phase is required for mitotic nuclear lamina disassembly and entry into mitosis and that betaII PKC-mediated phosphorylation of nuclear lamin B is important in these events.
Thompson
L J
LJ
Sealy Center for Oncology and Hematology, University of Texas Medical Branch, Galveston, Texas 77555, USA.
Fields
A P
AP
D000470:Alkaloids; D053119:Benzophenanthridines; D016203:CDC2 Protein Kinase / Q000302:isolation & purification / Q000378:metabolism; D017489:CDC28 Protein Kinase, S cerevisiae / Q000302:isolation & purification / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002846:Chromatography, Affinity; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016195:G2 Phase; D018922:HL-60 Cells; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007700:Kinetics; D034921:Lamin Type B; D034882:Lamins; D008938:Mitosis; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D034921:Lamin Type B; D034882:Lamins; D009687:Nuclear Proteins; D010617:Phenanthridines; C016299:chelerythrine; D011493:Protein Kinase C; D016203:CDC2 Protein Kinase; D017489:CDC28 Protein Kinase, S cerevisiae