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Differential regulation of Akt/protein kinase B isoforms during cell cycle progression
Author(s) -
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
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.01.005
Subject(s) - akt1 , pleckstrin homology domain , protein kinase b , akt2 , cell growth , proto oncogene proteins c akt , microbiology and biotechnology , phosphatidylinositol , cell cycle , gene isoform , chemistry , kinase , phosphorylation , pi3k/akt/mtor pathway , signal transduction , biology , biochemistry , cell , gene
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.