Induction of NF-κB by the Akt PKB kinase

The serine/threonine kinase Akt (also known as protein kinase a, PKB) is activated by numerous growth-factor and immune receptors through lipid products of phosphatidylinositol (PI) 3-kinase, Akt can couple to pathways that regulate glucose metabolism or cell survival [1], Akt can also regulate several transcription factors, including E2F, CREB, and the Forkhead family member Daf-16 [2-4], Here, we show that Akt can regulate signaling pathways that lead to induction of the NF-kappa B family of transcription factors in the Jurkat T-cell line, This induction occurs, at least in part, at the level of degradation of the NF-KB inhibitor I kappa B, and is specific for NF-kappa B, as other inducible transcription factors are not affected by Akt overexpression, Furthermore, the effect requires the kinase activity and pleckstrin homology (PH) domain of Akt, Also, Akt does not act alone to induce cytokine promoters and NF-kappa B reporters, because signals from other pathways are required to observe the effect. These studies uncover a previously unappreciated connection between Akt and NF-KB induction that could have implications for the control of T-cell growth and survival.