The ζ 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 ϵ and β

Abstract 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 TS1β and TS2αβ cell lines which can be maintained in interleukin-2, 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 γ chain of interleukin-2, 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 ζ and ϵ protein kinase C isoforms are involved in signaling through high-affinity interleukin-2 receptor and β and ζ are involved in signaling through intermediate-affinity interleukin-2 receptor. Taken together, our data indicate that activation of the ζ, β, and ϵ protein kinase C isoforms is an important step in interleukin-2-mediated proliferation.