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

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

doi:10.1016/j.febslet.2009.01.005

« Previous Next »FEBS Letters
Volume 583, Issue 4 , Pages 685-690, 18 February 2009

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

Edited by Angel Nebreda

Sung Ji Yun
- 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
David F. Tucker
- University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Eun Kyoung Kim
- 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
Min Sung Kim
- 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
Kee Hun Do
- 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
Jung Min Ha
- 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
Sun Young Lee
- 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
Jeanho Yun
- Department of Biochemistry, College of Medicine, Dong-A University, Republic of Korea
Chi Dae Kim
- 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
Morris J. Birnbaum
- University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
Sun Sik Bae
- 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
- Corresponding author. Fax: +82 51 244 1036.

Received 17 October 2008; received in revised form 22 December 2008; accepted 11 January 2009. published online 21 January 2009.

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.

Abbreviations: 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