Shojaiefard Manzar, Strutz-Seebohm Nathalie, Tavaré Jeremy M, Seebohm Guiscard, Lang Florian
Department of Physiology I, University of Tübingen, Germany.
Biochem Biophys Res Commun. 2007 Aug 10;359(4):843-7. doi: 10.1016/j.bbrc.2007.05.111. Epub 2007 May 25.
The Na(+), glucose cotransporter SGLT1 (SLC5A1) accomplishes Na(+)-dependent concentrative cellular glucose uptake. SGLT1 activity is enhanced by the serum and glucocorticoid inducible kinase SGK1. As shown recently, the stimulating effect of protein kinase B on the glucose carrier GLUT4 involves the mammalian phosphatidylinositol-3-phosphate-5-kinase PIKfyve (PIP5K3). The present experiments thus explored whether PIKfyve is similarly involved in the SGK1-dependent regulation of SLC5A1. In Xenopus oocytes expressing SLC5A1 but not in water injected oocytes glucose induced a current which was significantly enhanced by coexpression of PIKfyve. The effect of PIKfyve on SLC5A1 was blunted by additional coexpression of the inactive mutant of the serum and glucocorticoid inducible kinase (K119N)SGK1 and mimicked by coexpression of constitutively active (S422D)SGK1. The stimulating effect of PIKfyve was abrogated by replacement of the serine in the SGK consensus sequence by alanine ((S138A)PIKfyve). Moreover, coexpression of (S138A)PIKfyve significantly blunted the effect of SGK1 on SLC5A1 activity. The observations disclose that PIKfyve participates in the SGK1-dependent regulation of SLC5A1.
钠离子-葡萄糖共转运蛋白SGLT1（SLC5A1）实现了钠离子依赖的细胞对葡萄糖的浓缩摄取。血清和糖皮质激素诱导激酶SGK1可增强SGLT1的活性。最近的研究表明，蛋白激酶B对葡萄糖载体GLUT4的刺激作用涉及哺乳动物磷脂酰肌醇-3-磷酸-5-激酶PIKfyve（PIP5K3）。因此，本实验探究了PIKfyve是否同样参与SGK1对SLC5A1的依赖性调节。在表达SLC5A1的非洲爪蟾卵母细胞中，而非在注射水的卵母细胞中，葡萄糖可诱导产生电流，共表达PIKfyve可显著增强该电流。血清和糖皮质激素诱导激酶（K119N）SGK1的无活性突变体的额外共表达可减弱PIKfyve对SLC5A1的作用，而组成型活性（S422D）SGK1的共表达则可模拟该作用。将PIKfyve的SGK共有序列中的丝氨酸替换为丙氨酸（（S138A）PIKfyve）可消除PIKfyve的刺激作用。此外，（S138A）PIKfyve的共表达可显著减弱SGK1对SLC5A1活性的作用。这些观察结果表明，PIKfyve参与了SGK1对SLC5A1的依赖性调节。
