Differential regulation of Akt/protein kinase B isoforms during cell cycle progression

Phosphatidylinositol 3-kinase pathways play key regulatory roles in cell cycle progression into S phase. In this study, we demonstrated that Akt1/PKBα isoform plays an essential role in G1/S transition and proliferation. Cells lacking Akt1/PKBα showed an attenuated proliferation as well as G1/S transition, whereas cells lacking Akt2/PKBβ showed normal proliferation and G1/S transition. The effect of Akt1/PKBα on cell proliferation and G1/S transition was completely abolished by swapping pleckstrin homology (PH) domain with that of Akt2/PKBβ. Finally, full activation of Akt/PKB and cyclin D expression was achieved by the Akt1/PKBα or chimeric proteins containing the PH domain of Akt1/PKBα indicating that the PH domain of Akt1/PKBα provides full kinase activity and is necessary for the G1/S transition.