IMPLICATION OF PROTEIN-KINASE-C IN IL-2-MEDIATED PROLIFERATION AND APOPTOSIS IN A MURINE T-CELL CLONE

Several reports have suggested that protein kinase C plays an essentia l role in T cell activation and apoptosis. The recent synthesis of the selective protein kinase C inhibitor, GF109203X, has made it possible to test the relevance of protein kinase C in T cell proliferation and apoptosis. We report that the use of GF 109203X, in concentrations th at are below its toxicity limits, inhibits IL-2-dependent proliferatio n in murine T cells expressing intermediate or high-affinity IL-2R (TS 1 beta and TS1 alpha beta). In addition, GF109203X reverts the suppres sion of apoptosis mediated by IL-2 or IL-2 + dexamethasone. The use of the phorbol ester PMA, a protein kinase C activator, allows a bypass of the IL-2/IL-2R interaction in the suppression of apoptosis mediated by dexamethasone or IL-2 withdrawal in TS1 beta cells but not in TS1 alpha beta cells. Taken together, our data indicate that activation of protein kinase C is an important step in IL-2-mediated proliferation and in suppression of apoptosis. (C) 1994 Academic Press, Inc.