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/PKBalpha isoform plays an essential role in G(1)/S transition and proliferation. Cells lacking Akt1/PKBalpha showed an attenuated proliferation as well as G(1)/S transition, whereas cells lacking Akt2/PKBbeta showed normal proliferation and G(1)/S transition. The effect of Akt1/PKBalpha on cell proliferation and G(1)/S transition was completely abolished by swapping pleckstrin homology (PH) domain with that of Akt2/PKBbeta. Finally, full activation of Akt/PKB and cyclin D expression was achieved by the Akt1/PKBalpha or chimeric proteins containing the PH domain of Akt1/PKBalpha indicating that the PH domain of Akt1/PKBalpha provides full kinase activity and is necessary for the G(1)/S transition.
Yun
Sung Ji
SJ
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.
Tucker
David F
DF
Kim
Eun Kyoung
EK
Kim
Min Sung
MS
Do
Kee Hun
KH
Ha
Jung Min
JM
Lee
Sun Young
SY
Yun
Jeanho
J
Kim
Chi Dae
CD
Birnbaum
Morris J
MJ
Bae
Sun Sik
SS
D000818:Animals; D002453:Cell Cycle; D049109:Cell Proliferation; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004622:Embryo, Mammalian; D004789:Enzyme Activation; D005347:Fibroblasts / Q000166:cytology* / Q000201:enzymology*; D005456:Fluorescent Dyes / Q000378:metabolism; D016193:G1 Phase; D015971:Gene Expression Regulation, Enzymologic; D007211:Indoles / Q000378:metabolism; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051057:Proto-Oncogene Proteins c-akt / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D012190:Retroviridae / Q000235:genetics; D016196:S Phase; D013997:Time Factors
D016895:Culture Media, Serum-Free; D005456:Fluorescent Dyes; D007211:Indoles; D020033:Protein Isoforms; C007293:DAPI; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt