PKBα is required for adipose differentiation of mouse embryonic fibroblasts
PKBα is required for adipose differentiation of mouse embryonic fibroblasts
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DOI：
10.1242/jcs.02792
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发表时间：
2006-03-01
影响因子：
4
通讯作者：
Hemmings, BA
中科院分区：
文献类型：
--
作者：
Baudry, A;Yang, ZZ;Hemmings, BA
蛋白激酶Bot（PKB α）是代谢、增殖和分化的关键调节剂。我们使用野生型和PKB α基因敲除小鼠胚胎成纤维细胞（MEFs）探索了PKB α在脂肪形成中的作用，并表明缺乏PKBa会阻止MEFs分化为脂肪细胞。PKB α缺陷细胞中异位PKB α的表达恢复脂肪形成。我们确定了80个基因，其表达在脂肪形成过程中在野生型MEFs中上调，但在相同条件下，其表达在PKBa缺陷的MEFs中显著降低。值得注意的是，脂肪形成Kruppel样转录因子15基因表达的调节剂在PKb α缺陷的MEFs中下调，但可以通过在缺陷细胞中表达活性PKB α来恢复。脂肪细胞表达的脂质运载蛋白2、肾素1和受体活性修饰蛋白3基因的水平在PKB α缺陷的MEFs中也降低，并且在3 T3-L1细胞的早期脂肪细胞分化期间被LY 294002处理抑制。结果强调了PKBa在脂肪形成所需的转录程序中的重要作用。
Protein kinase Bot (PKB alpha.) is a key regulator of metabolism, proliferation and differentiation. We have explored the role of PKB alpha in adipogenesis using wild-type and PKB alpha-knockout mouse embryonic fibroblasts (MEFs) and show that lack of PKBa prevents MEF differentiation into adipocytes. Expression of ectopic PKB alpha in PKB alpha-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 PKBa-deficient MEFs under the same conditions. Significantly, the regulator of adipogenesis Kruppel-like transcription factor 15 gene expression was downregulated in PKb alpha-deficient MEFs but could be restored by expressing an active PKB alpha 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 PKB alpha-deficient MEFs, and are inhibited by LY294002 treatment during early adipocyte differentiation of 3T3-L1 cells. The results underscore an essential role for PKBa in the transcriptional program required for adipogenesis.