Isoform-specific regulation of adipocyte differentiation by Akt/protein kinase Balpha.
The phosphatidylinositol 3-kinase (PI3K)/Akt pathway tightly regulates adipose cell differentiation. Here we show that loss of Akt1/PKBalpha in primary mouse embryo fibroblast (MEF) cells results in a defect of adipocyte differentiation. Adipocyte differentiation in vitro and ex vivo was restored in cells lacking both Akt1/PKBalpha and Akt2/PKBbeta by ectopic expression of Akt1/PKBalpha but not Akt2/PKBbeta. Akt1/PKBalpha was found to be the major regulator of phosphorylation and nuclear export of FoxO1, whose presence in the nucleus strongly attenuates adipocyte differentiation. Differentiation-induced cell division was significantly abrogated in Akt1/PKBalpha-deficient cells, but was restored after forced expression of Akt1/PKBalpha. Moreover, expression of p27(Kip1), an inhibitor of the cell cycle, was down regulated in an Akt1/PKBalpha-specific manner during adipocyte differentiation. Based on these data, we suggest that the Akt1/PKBalpha isoform plays a major role in adipocyte differentiation by regulating FoxO1 and p27(Kip1).
Yun
Sung-Ji
SJ
Medical Research Center 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.
Kim
Eun-Kyoung
EK
Tucker
David F
DF
Kim
Chi Dae
CD
Birnbaum
Morris J
MJ
Bae
Sun Sik
SS
D017667:Adipocytes / Q000166:cytology* / Q000201:enzymology*; D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D002455:Cell Division / Q000235:genetics; D002478:Cells, Cultured; D002999:Clone Cells / Q000201:enzymology; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000032:analysis / Q000378:metabolism; D008297:Male; D051379:Mice; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*
D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D020033:Protein Isoforms; D051057:Proto-Oncogene Proteins c-akt