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.