Analysis of the role of protein kinase C-α, -ε, and -ζ 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 PKC isotypes. To address this issue, mutationally active PKC-α, -ε, or -ζ 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-ε and, to a lesser extent PKC-α but not -ζ, can regulate the transcription factors AP-1 and nuclear factor of activated T cells (NF-AT-1). The ability of PKC-ε to induce transactivation of NF-AT-1 and AP-1 was similar to the stimulatory effect of a constitutively activated p21^ras. PKC-ε, but not PKC-α 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 Ras and PKC mutants suggest that PKC-α, p21^ras, and PKC-ε are not positioned linearly on a single signal transduction pathway.