Serum and glucocorticoid-regulated kinase Sgk1 inhibits insulin-dependent activation of phosphomannomutase 2 in transfected COS-7 cells
Serum and glucocorticoid-regulated kinase Sgk1 inhibits insulin-dependent activation of phosphomannomutase 2 in transfected COS-7 cells
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DOI：
10.1152/ajpcell.00284.2004
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发表时间：
2005-01-01
影响因子：
5.5
通讯作者：
Perrotti, N
中科院分区：
文献类型：
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作者：
Menniti, M;Iuliano, R;Perrotti, N
血清和糖皮质激素调节激酶（Sgk1）被认为是一个重要的汇合点肽和类固醇调节ENaC介导的钠转运。我们尝试通过酵母双杂交筛选Sgk1的分子伴侣。酵母双杂交筛选表明，Sgk1和磷酸甘露变位酶（PMM）2，其中后者是一种参与糖蛋白生物合成的调节酶之间的特定相互作用。通过共免疫沉淀和共聚焦显微镜检测，在完整细胞中证实了相互作用。然后，我们能够证明，在体外试验中，Sgk1磷酸化PMM2。此外，我们发现，PMM2的酶活性上调胰岛素治疗和Sgk1完全抑制PMM2的活性，无论是在缺乏和存在胰岛素刺激。这些数据提供的证据表明，Sgk1可能调节胰岛素作用的糖蛋白的共翻译糖基化。
Serum- and glucocorticoid-regulated kinase (Sgk1) is considered to be an essential convergence point for peptide and steroid regulation of ENaC-mediated sodium transport. We tried to identify molecular partners of Sgk1 by yeast two-hybrid screening. Yeast two-hybrid screening showed a specific interaction between Sgk1 and phosphomannomutase (PMM) 2, the latter of which is an enzyme involved in the regulation of glycoprotein biosynthesis. The interaction was confirmed in intact cells by coimmunoprecipitation and colocalization detected using confocal microscopy. We were then able to demonstrate that Sgk1 phosphorylated PMM2 in an in vitro assay. In addition, we found that the enzymatic activity of PMM2 is upregulated by insulin treatment and that Sgk1 completely inhibits PMM2 activity both in the absence and in the presence of insulin stimulation. These data provide evidence suggesting that Sgk1 may modulate insulin action on the cotranslational glycosylation of glycoproteins.