Complex Formation and Cooperation of Protein Kinase Cθ and Akt1/Protein Kinase Bα in the NF-κB Transactivation Cascade in Jurkat T Cells

Abstract

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