AKT1/PKBα is recruited to lipid rafts and activated downstream of PKC isotypes in CD3-induced T cell signaling

Abstract

Protein kinase (PK) Cθ and Akt/PKBα cooperate in T cell receptor/CD28-induced T cell signaling. We here demonstrate the recruitment of endogenous Akt1 and PKCθ to lipid rafts in CD3-stimulated T cells. Further we show that Myr-PKCθ mediates translocation of endogenous Akt1 to the plasma membrane as well as to lipid rafts, most likely explained by the observed complex formation of both protein kinases. In addition, in peripheral mouse T cells, the PKC inhibitor Gö6850 could partially block Akt1 activation in CD3-induced signaling, placing PKC isotype(s) upstream of Akt1. However, T cells derived from PKCθ knockout mice were not impaired in CD3- or phorbol ester-induced Akt1 activity. Taken together, the results of this study give new insights into the functional link of Akt1 and PKCθ in T cell signaling, demonstrating the co-recruitment of the two kinases and showing a novel pathway leading to Akt1 transactivation where PKC isotype(s) are involved but PKCθ is not essential.