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Differential regulation of Akt/protein kinase B isoforms during cell cycle progression |
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| Authors: | Sung Ji Yun Eun Kyoung Kim Kee Hun Do Sun Young Lee Chi Dae Kim Sun Sik Bae |
| Affiliation: | a MRC for Ischemic Tissue Regeneration and Medical Research Institute, Department of Pharmacology, School of Medicine, Pusan National University, Ami-dong 1-ga 10, Seo-gu, Busan 602-739, Republic of Korea b University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA c Department of Biochemistry, College of Medicine, Dong-A University, Republic of Korea |
| Abstract: | 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. |
| Keywords: | MEF, mouse embryo fibroblast PI3K, phosphatidylinositol 3-kinase PtdIns-(3,4,5)P3, phosphatidylinositol 3,4,5-trisphosphate PTEN, phosphatase and tensin homolog PKB, protein kinase B PH, pleckstrin homology mTOR, mammalian target of rapamycin |
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