Complex formation and cooperation of protein kinase Cθ and Akt1/protein kinase Bα in the NF-κB transactivation cascade in Jurkat T cells

Protein kinase C theta (PKC theta) is known to induce NF-kappaB, an essential transcriptional element in T cell receptor/ CD28-mediated interleukin-2 production but also T cell survival. Here we provide evidence that PKC theta is physically and functionally coupled to Akt1 in this signaling pathway. First, T cell receptor/CD3 ligation was sufficient to induce activation as well as plasma membrane recruitment of PKC theta. Second, PKC theta selectively cooperated with Akt1, known to act downstream of CD28 coreceptor signaling, in activating a NF-kappaB reporter in T cells. Third, Akt1 function was shown to be required for PKC theta -mediated NF-kappaB transactivation. Fourth, PKC theta co-immunoprecipitated with Akt1 however, neither Akt1 nor PKC theta served as a prominent substrate for each other in vitro as well as in intact T cells. Finally, plasma membrane targeting of PKC theta and Akt1 exerted synergistic transactivation of the I-kappaB kinase beta /inhibitor of NF-kappaB/NF-kappaB signaling cascade independent of T cell activation. Taken together, these findings suggest a direct cross-talk between PKC theta and Akt1 in Jurkat T cells.