Protein kinase C, a coupling element between stimulus and secretion of basophils.
Protein kinase C plays a crucial role in the transmission and control of secretory cell membranal signals. This Ca2+ and phospholipid dependent kinase have been isolated and partially purified from histamine secreting rat basophilic leukemia cells (RBL-2H3 line). The tumor promoter 12-O-tetradecanoyl phorbol-13-acetate ester (TPA) directly activated this isolated enzyme. In the intact RBL-2H3 cells, TPA did not significantly affect free intracellular Ca2+ ions concentration or induce secretion. However, at low concentrations it synergistically enhanced secretion induced either by antigen or ionophore. Significantly, at TPA concentrations exceeding 25 ng/ml both the increase in cytosolic free Ca2+ and the ensuing degranulation were inhibited. The synergism between TPA and the ionophore reaches saturation. These findings suggest that free cytosolic Ca2+ and kinase C-mediated protein phosphorylation are synergistically involved in the mediation of the cellular response. Moreover, kinase C appears to play a dual role both in the activation and termination of secretion. The latter is most probably achieved by closure of the Ca2+ channels in the cells.
D000818:Animals; D001491:Basophils / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D007942:Leukemia, Experimental / Q000503:physiopathology; D010766:Phosphorylation; D011493:Protein Kinase C; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D011494:Protein Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium