Potentiation of insulin-induced phosphatidylinositol-3 kinase activity by phorbol ester is mediated by protein kinase C epsilon.
Our previous results have demonstrated that phorbol 12-myristate 13-acetate (TPA) and insulin synergistically stimulate the activity of phosphatidylinositol-3 kinase (PI-3 kinase) and PI-3 kinase plays an important role in both of TPA-induced AP-1 activation and cell transformation in tumour promotion sensitive (P+) JB6 cells. In the present study, we investigated the role of PKC and its isozymes in the synergistic induction of PI-3 kinase by TPA and insulin. Bisindolylmaleimide inhibits TPA- and TPA+ insulin-induced PI-3 kinase activity. Pretreatment of cells for 24 h with TPA has significant inhibitory effects on TPA-induced PI-3 kinase activity and abolishes the synergistic effect of TPA and insulin-stimulated PI-3 kinase activity. Furthermore, overexpression of a dominant negative PKC epsilon, but not dominant negative PKC alpha, blocks the synergistic effect of TPA and insulin-induced PI-3 kinase activity. These results indicate that the potentiation effect of TPA on insulin-induced PI-3 kinase activity is specific through PKC epsilon in JB6 cells.
Huang
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Hormel Institute, University of Minnesota, Austin 55912, USA.
Ma
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WY
Dong
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D000818:Animals; D002460:Cell Line; D004357:Drug Synergism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000078404:Epidermal Cells; D004817:Epidermis / Q000201:enzymology; D007211:Indoles / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008301:Maleimides / Q000494:pharmacology; D051379:Mice; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007211:Indoles; D007328:Insulin; D007527:Isoenzymes; D008301:Maleimides; D019869:Phosphatidylinositol 3-Kinases; C497256:Prkce protein, mouse; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; C088060:bisindolylmaleimide; D013755:Tetradecanoylphorbol Acetate