Jeyaraj Sankarganesh, Boehmer Christoph, Lang Florian, Palmada Monica
Institute of Physiology I, University of Tübingen, 72076 Tübingen, Germany.
Biochem Biophys Res Commun. 2007 May 11;356(3):629-35. doi: 10.1016/j.bbrc.2007.03.029. Epub 2007 Mar 12.
Insulin stimulates glucose transport into muscle and fat cells by enhancing GLUT4 abundance in the plasma membrane through activation of phosphatidylinositol 3-kinase (PI3K). Protein kinase B (PKB) and PKCzeta are known PI3K downstream targets in the regulation of GLUT4. The serum- and glucocorticoid-inducible kinase SGK1 is similarly activated by insulin and capable to regulate cell surface expression of several metabolite transporters. In this study, we evaluated the putative role of SGK1 in the modulation of GLUT4. Coexpression of the kinase along with GLUT4 in Xenopus oocytes stimulated glucose transport. The enhanced GLUT4 activity was paralleled by increased transporter abundance in the plasma membrane. Disruption of the SGK1 phosphorylation site on GLUT4 ((S274A)GLUT4) abrogated the stimulating effect of SGK1. In summary, SGK1 promotes glucose transporter membrane abundance via GLUT4 phosphorylation at Ser274. Thus, SGK1 may contribute to the insulin and GLUT4-dependent regulation of cellular glucose uptake.
胰岛素通过激活磷脂酰肌醇3激酶（PI3K），增加质膜中葡萄糖转运蛋白4（GLUT4）的丰度，从而刺激葡萄糖转运进入肌肉和脂肪细胞。蛋白激酶B（PKB）和蛋白激酶Cζ（PKCζ）是PI3K在调节GLUT4中的已知下游靶点。血清和糖皮质激素诱导激酶SGK1同样被胰岛素激活，并能够调节几种代谢物转运体的细胞表面表达。在本研究中，我们评估了SGK1在调节GLUT4中的假定作用。该激酶与GLUT4在非洲爪蟾卵母细胞中共表达可刺激葡萄糖转运。GLUT4活性增强的同时质膜中转运体丰度增加。GLUT4上SGK1磷酸化位点的破坏（(S274A)GLUT4）消除了SGK1的刺激作用。总之，SGK1通过在Ser274处对GLUT4进行磷酸化促进葡萄糖转运体在膜上的丰度。因此，SGK1可能有助于胰岛素和GLUT4依赖性的细胞葡萄糖摄取调节。
