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 G 1/S transition and proliferation. Cells lacking Akt1/ PKBα showed an attenuated proliferation as well as G 1/S t...

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Veröffentlicht in:	FEBS letters 2009-02, Vol.583 (4), p.685-690
Hauptverfasser:	Yun, Sung Ji, Tucker, David F., Kim, Eun Kyoung, Kim, Min Sung, Do, Kee Hun, Ha, Jung Min, Lee, Sun Young, Yun, Jeanho, Kim, Chi Dae, Birnbaum, Morris J., Bae, Sun Sik
Format:	Artikel
Sprache:	eng
Schlagworte:	Akt/protein kinase B Animals Cell Cycle Cell Proliferation Cells, Cultured Culture Media, Serum-Free Embryo, Mammalian Enzyme Activation Fibroblasts - cytology Fibroblasts - enzymology Fluorescent Dyes - metabolism G1 Phase Gene Expression Regulation, Enzymologic Indoles - metabolism mammalian target of rapamycin MEF Mice mouse embryo fibroblast mTOR phosphatase and tensin homolog phosphatidylinositol 3,4,5-trisphosphate Phosphatidylinositol 3-kinase Phosphatidylinositol 3-Kinases - metabolism PI3K PKB pleckstrin homology Proliferation Protein Isoforms - genetics Protein Isoforms - metabolism protein kinase B Protein Structure, Tertiary Proto-Oncogene Proteins c-akt - chemistry Proto-Oncogene Proteins c-akt - deficiency Proto-Oncogene Proteins c-akt - metabolism PtdIns-(3,4,5)P3 PTEN Retroviridae - genetics S Phase Time Factors
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Zusammenfassung:	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 G 1/S transition and proliferation. Cells lacking Akt1/ PKBα showed an attenuated proliferation as well as G 1/S transition, whereas cells lacking Akt2/ PKBβ showed normal proliferation and G 1/S transition. The effect of Akt1/PKBα on cell proliferation and G 1/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 G 1/S transition.
ISSN:	0014-5793 1873-3468
DOI:	10.1016/j.febslet.2009.01.005