Nuclear protein kinase C activity is decreased in Friend erythroleukemia cells induced to differentiate.
Although it is well known that protein kinase C (PKC) is an important signaling molecule in Friend erythroleukemia cells it is not clear what role PKC may play in either regulated or unregulated erythroid cell proliferation and differentiation. The purpose of this study was to test the hypothesis that a decrease in nuclear PKC activity is associated with the induction of differentiation in Friend erythroleukemia cells. The effects of staurosporine, a selective inhibitor of PKC, and the tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate, an activator of PKC, on Friend cell proliferation and differentiation were examined. Neither the inhibitor nor the activator of PKC affected proliferation at 96 h as measured by [3H]thymidine incorporation, but both compounds inhibited cell differentiation. In addition, nuclear PKC activity was highest in untreated and in tumor promoter-treated cells that were not differentiated, and it was lowest in cells induced to differentiate with hexamethylene bisacetamide or dimethylsulfoxide. It is concluded that nuclear PKC activity is essential for Friend erythroleukemia cell proliferation, and that a decrease in enzyme activity within the nucleus is associated with differentiation.
Beckman
B S
BS
Tulane University School of Medicine, Department of Pharmacology, New Orleans, LA 70112.
D000081:Acetamides / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002467:Cell Nucleus / Q000201:enzymology*; D002472:Cell Transformation, Viral / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D005622:Friend murine leukemia virus; D006397:Hematinics / Q000494:pharmacology; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology / Q000382:microbiology / Q000473:pathology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology / Q000473:pathology
D000081:Acetamides; D000470:Alkaloids; D006397:Hematinics; D014316:Tritium; D004247:DNA; D011493:Protein Kinase C; D019311:Staurosporine; C014026:hexamethylene bisacetamide; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine; D004121:Dimethyl Sulfoxide