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/PKB alpha isoform plays an essential role in G(1)/S transition and proliferation. Cells lacking Akt1/PKB alpha showed an attenuated proliferation as well as G(1)/S transition, whereas cells lacking Akt2/PKB beta showed normal proliferation and G(1)/S transition. The effect of Akt1/PKB alpha on cell proliferation and G(1)/S transition was completely abolished by swapping pleckstrin homology (PH) domain with that of Akt2/PKB beta. Finally, full activation of Akt/PKB and cyclin D expression was achieved by the Akt1/PKB alpha or chimeric proteins containing the PH domain of Akt1/PKB alpha indicating that the PH domain of Akt1/PKB alpha provides full kinase activity and is necessary for the G(1)/S transition. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.