ANALYSIS OF THE ROLE OF PROTEIN-KINASE-C-ALPHA, PROTEIN-KINASE-EPSILON, AND PROTEIN-KINASE-ZETA IN T-CELL ACTIVATION

T cells express multiple isotypes of protein kinase C (PKC) and although it is well accepted that PKCs have an important role in T cell activation, little is known about the function of individual PRC isotypes. To address this issue, mutationally active PKC-alpha, -epsilon, or -zeta have been transfected into T cells and the consequences for T cell activation determined, p21(ras) plays an essential role in T cell activation, Accordingly, the effects of the constitutively active PKCs were compared to the effects of mutationally activated p21(ras), The data indicate that PKC-epsilon and, to a lesser extent PKC-alpha but not -zeta can regulate the transcription factors AP-1 and nuclear factor of activated T cells (NF-AT-1), The ability of PKC-epsilon to induce transactivation of NF-AT-1 and AP-I was similar to the stimulatory effect of a constitutively activated p21(ras), PKC-epsilon, but not PKC-alpha nor activated p21(ras), was able to induce NF-KB activity, Phorbol esters induce expression of CD69 whereas none of the activated PKC isotypes tested were able to have this effect. Activated Src and p21(ras) were able to induce CD69 expression. These results indicate selective functions for different PKC isotypes in T cells. Moreover, the data comparing the effects of activated has and PKC mutants suggest that PKC-alpha, p21(ras), and PKC-epsilon are not positioned linearly on a single signal transduction pathway.