PKBalpha is required for adipose differentiation of mouse embryonic fibroblasts.
Protein kinase Balpha (PKBalpha) is a key regulator of metabolism, proliferation and differentiation. We have explored the role of PKBalpha in adipogenesis using wild-type and PKBalpha-knockout mouse embryonic fibroblasts (MEFs) and show that lack of PKBalpha prevents MEF differentiation into adipocytes. Expression of ectopic PKBalpha in PKBalpha-deficient cells restores adipogenesis. We identified 80 genes whose expression was upregulated in wild-type MEFs during adipogenesis but whose expression was significantly reduced in PKBalpha-deficient MEFs under the same conditions. Significantly, the regulator of adipogenesis Krüppel-like transcription factor 15 gene expression was downregulated in PKBalpha-deficient MEFs but could be restored by expressing an active PKBalpha in the deficient cells. The level of lipocalin 2, renin 1 and receptor-activity-modifying protein 3 genes expressed by adipose cells was also decreased in PKBalpha-deficient MEFs, and are inhibited by LY294002 treatment during early adipocyte differentiation of 3T3-L1 cells. The results underscore an essential role for PKBalpha in the transcriptional program required for adipogenesis.
Friedrich Miescher Institute for Biomedical Research, Maulbeerstr. 66, CH-4058, Basel, Switzerland.
Anne
A
Baudry
Zhong-Zhou
ZZ
Yang
Brian A
BA
Hemmings
D000209:Acute-Phase Proteins / Q000187:drug effects / Q000235:genetics; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D050156:Adipogenesis / Q000187:drug effects / Q000502:physiology; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020869:Gene Expression Profiling; D047908:Intracellular Signaling Peptides and Proteins / Q000187:drug effects / Q000235:genetics; D000071068:Lipocalin-2; D054834:Lipocalins; D008565:Membrane Proteins / Q000187:drug effects / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009025:Morpholines / Q000494:pharmacology; D015513:Oncogene Proteins / Q000187:drug effects / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000172:deficiency / Q000187:drug effects / Q000502:physiology*; D058261:Receptor Activity-Modifying Proteins; D012083:Renin / Q000187:drug effects / Q000235:genetics
D000209:Acute-Phase Proteins; D051792:Basic Helix-Loop-Helix Proteins; D002867:Chromones; D047908:Intracellular Signaling Peptides and Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D008565:Membrane Proteins; D009025:Morpholines; D015513:Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D058261:Receptor Activity-Modifying Proteins; D012083:Renin; C093234:Tcf15 protein, mouse; C071332:Lcn2 protein, mouse; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one