Opposing Effects of Protein Kinase C on IgE-Dependent Exocytosis and InsP3 Formation
Aggregation of the receptors for Immunoglobulin E (IgE) by a multivalent antigen (Ag) leads to activation of phospholipase C (PLC) and secretion of serotonin from Rat Basophilic Leukemia (RBL) cells. The phorbol ester 12-0-tetradecanoyl-phorbol-13-acetate (TPA), exerts dual actions on the IgE-dependent responses in RBL cells: TPA potentiates IgE- induced secretion but it inhibits IgE-induced InsP3 formation and the subsequent rise in internal Ca2+ concentrations. In addition, TPA synergizes with Ca2+ ionophores to trigger exocytosis. We have undertaken this study to examine whether the dual actions of TPA are both mediated by protein kinase C (PKC). It is relevant to evaluate the participation of PKC in TPA actions since some reports suggest that not all TPA actions are consequences of TPA binding and activation of PKC (Zick et al. (1985); Maraganore, J.M. (1987)). In addition, PKC consists of a family of enzymes that while closely related in structure (reviewed in Nishizuka, Y. (1988)), they differ in their cellular and intracellular disributions as well as in their responses to cofactors such as Ca2+, diacylglycerol (DAG), phosphatidylserine (PS) and fatty acids (Nishizuka, Y. (1988)). We have therefore analyzed the possibility that different isozymes of PKC may be involved in mediating the opposing effects of TPA on the IgE-mediated responses in RBL cells.
KeywordsDual Action Serotonin Secretion Multivalent Antigen Phorbol Dibutyrate Active Phorbol Ester
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