THE ZETA-ISOFORM OF PROTEIN-KINASE-C CONTROLS INTERLEUKIN-2-MEDIATED PROLIFERATION IN A MURINE T-CELL LINE - EVIDENCE FOR AN ADDITIONAL ROLE OF PROTEIN-KINASE-C-EPSILON AND PROTEIN-KINASE-C-BETA

In order to address a role of protein kinase C in signal transduction through interleukin-2, interleukin-4, and interleukin-9 receptors, we took advantage of the availability of a selective protein kinase C inhibitor, GF109203X, and the availability of TS1 beta and TS1 alpha beta cell lines which can be maintained in interleukin-a, interleukin-4, or interleukin-9 independently. In this report we report that inhibition of protein kinase C activity by GF109203X does not block interleukin-4- or interleukin-9-dependent proliferation and, on the contrary, does block interleukin-2-dependent proliferation, suggesting that interleukin-4 and interleukin-9 do not use signal transduction pathways mediated by protein kinase C and that the common gamma chain of interleukin-a, interleukin-4, and interleukin-9 receptors is not responsible per se for the activation of protein kinase C through interleukin-2 receptor. Moreover, GF109203X induces apoptosis in cells cultured in interleukin-2 but not in interleukin-4 or interleukin-9. Using antisense oligonucleotides, we report that the zeta and epsilon protein kinase C isoforms are involved in signaling through high-affinity interleukin-a receptor and beta and zeta are involved in signaling through intermediate-affinity interleukin-a receptor. Taken together, our data indicate that activation of the zeta, beta, and epsilon protein kinase C isoforms is an important step in interleukin-2-mediated proliferation. (C) 1995 Academic Press, Inc.