Regulation of GLUT1 gene transcription by the serine threonine kinase Akt1
Regulation of GLUT1 gene transcription by the serine threonine kinase Akt1
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DOI：
10.1074/jbc.274.29.20281
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发表时间：
1999-07-16
影响因子：
4.8
通讯作者：
Roth, RA
中科院分区：
文献类型：
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作者：
Barthel, A;Okino, ST;Roth, RA
我们利用小鼠肝癌细胞(Hepa1c1c7)研究了丝氨酸/苏氨酸激酶Akt在诱导GLUT1基因表达中的作用。为了选择性地激活Akt激酶级联，我们在Hepa1c1c7细胞中表达了一种可调节的Akt(Myristoylated Akt1雌激素受体嵌合体，Mer-Akt1)；我们证实了羟三苯氧胺刺激mer-Akt1活性的程度与胰岛素激活内源性Akt的程度相似。我们的研究表明，羟基他莫昔芬刺激mer-Akt1诱导GLUT1的mRNA和蛋白积累到与胰岛素诱导的水平相当；因此，Akt级联反应的激活足以诱导该细胞系统中GLUT1基因的表达。此外，蛋白激酶失活Akt突变体的表达部分抑制了GLUT1基因对胰岛素的反应。进一步的研究表明，Akt和胰岛素诱导的GLUT1 mRNA反映了mRNA合成的增加，而不是减少了mRNA的降解。我们的发现表明，GLUT1基因在转录水平上对胰岛素做出反应，Akt在该系统中介导了GLUT1基因表达的激活步骤。
We used mouse hepatoma (Hepa1c1c7) cells to study the role of the serine/threonine kinase Akt in the induction of GLUT1 gene expression. In order to selectively turn on the Akt kinase cascade, we expressed a hydroxytamoxifen-regulatable form of Akt (myristoylated Akt1 estrogen receptor chimera (MER-Akt1)) in the Hepa1c1c7 cells; we verified that hydroxytamoxifen stimulates MER-Akt1 activity to a similar extent as the activation of endogenous Akt by insulin. Our studies reveal that stimulation of MER-Akt1 by hydroxytamoxifen induces GLUT1 mRNA and protein accumulation to levels comparable to that induced by insulin; therefore, activation of the Akt cascade suffices to induce GLUT1 gene expression in this cell system. Furthermore, expression of a kinase-inactive Akt mutant partially inhibits the response of the GLUT1 gene to insulin. Additional studies reveal that the induction of GLUT1 mRNA by Akt and by insulin reflects increased mRNA synthesis and not decreased mRNA degradation. Our findings imply that the GLUT1 gene responds to insulin at the transcriptional level and that Akt mediates a step in the activation of GLUT1 gene expression in this system.