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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Epithelial sodium channel regulated by aldosterone-induced protein sgk
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Epithelial sodium channel regulated by aldosterone-induced protein sgk

机译：醛固酮诱导的蛋白sgk调节上皮钠通道

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Sodium homeostasis in terrestrial and freshwater vertebrates is controlled by the corticosteroid hormones principally aldosterone, which stimulate electrogenic Na+ absorption in tight epithelia. Although aldosterone is known to increase apical membrane Na+ permeability in target ceIls through changes in gene transcription, the mechanistic basis of this effect remains poorly understood. The predominant early effect of aldosterone is to increase the activity of the epithelial sodium channel (ENaC), although ENaC mRNA and protein levels do not change initially. Rather, the open probability and/or number of channels in the apical membrane are greatly increased by unknown modulators. To identify hormone-stimulated gene products that modulate ENaC activity, a subtracted cDNA library was generated from A6 cells, a stable cell line of renal distal nephron origin, and the effect of candidates on ENaC activity was tested in a coexpression assay. We report here the identification of sgk (serum and glucocorticoid-regulated kinase), a member of the serine--threonine kinase family, as an aldosterone- induced regulator of ENaC activity. sgk mRNA and protein were strongly and rapidly hormone stimulated both in A6 cells and in rat kidney. Furthermore, sgk stimulated ENaC activity approximately 7-fold when they were coexpressed in Xenopus laevis oocytes. These data suggest that sgk pIays a central role in aldosterone regulation of Na+ absorption and thus in thc control of extracellular fluid volume, blood pressure, and sodium homeostasis.
机译：陆地和淡水脊椎动物中的钠稳态由皮质类固醇激素（主要是醛固酮）控制，该激素刺激紧密上皮细胞中的钠离子吸收。尽管已知醛固酮通过基因转录的变化增加靶细胞的顶膜Na +渗透性，但对该作用的机理基础仍知之甚少。醛固酮的主要早期作用是增加上皮钠通道（ENaC）的活性，尽管ENaC的mRNA和蛋白质水平最初并没有改变。而是，未知调节剂极大地增加了顶膜中的开放概率和/或通道数量。为了鉴定调节ENaC活性的激素刺激基因产物，从A6细胞，肾脏远端肾单位来源的稳定细胞系中生成了一个减去的cDNA文库，并在共表达测定中测试了候选物对ENaC活性的影响。我们在这里报告鉴定出sgk（血清和糖皮质激素调节的激酶），它是一种由醛固酮诱导的ENaC活性调节剂，是丝氨酸-苏氨酸激酶家族的成员。 sgk mRNA和蛋白在A6细胞和大鼠肾脏中均受到激素的强烈而迅速的刺激。此外，当它们在非洲爪蟾卵母细胞中共表达时，sgk刺激ENaC活性约为7倍。这些数据表明，sgk在醛固酮对Na +吸收的调节中，因此在对细胞外液量，血压和钠稳态的控制中起着中心作用。

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