sgk:: an essential convergence point for peptide and steroid hormone regulation of ENaC-mediated Na+ transport

被引:110
作者
Faletti, CJ
Perrotti, N
Taylor, SI
Blazer-Yost, BL
机构
[1] Indiana Univ Purdue Univ, Dept Biol, Indianapolis, IN 46202 USA
[2] NIDDKD, Diabet Branch, Div Intramural Res, Bethesda, MD 20892 USA
[3] Univ Catanzaro, Dipartimento Med Sperimentale & Clin G Salvatore, I-88100 Catanzaro, Italy
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2002年 / 282卷 / 03期
关键词
insulin; antidiuretic hormone; aldosterone; amiloride; phosphoinositide pathway; epithelial Na+ channel; serum and glucocortoid-induced kinase;
D O I
10.1152/ajpcell.00408.2001
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
To study the role of sgk (serum, glucocorticoid-induced kinase) in hormonal regulation of Na+ transport mediated by the epithelial Na+ channel (ENaC), clonal cell lines stably expressing human sgk, an S422A sgk mutant, or a D222A sgk mutant were created in the background of the A6 model renal epithelial cell line. Expression of normal sgk results in a 3.5-fold enhancement of basal transport and potentiation of the natriferic response to antidiuretic hormone (ADH). Transfection of a S422A mutant form of sgk, which cannot be phosphorylated by phosphatidylinositol-dependent kinase (PDK)-2, results in a cell line that is indistinguishable from the parent line in basal and hormone-stimulated Na+ transport. The D222A sgk mutant, which lacks kinase activity, functions as a dominant-negative mutant inhibiting basal as well as peptide- and steroid hormone- stimulated Na+ transport. Thus sgk activity is necessary for ENaC-mediated Na+ transport. Phosphorylation and activation by PDK-2 are necessary for sgk stimulation of ENaC. Expression of normal sgk over endogenous levels results in a potentiated natriferic response to ADH, suggesting that the enzyme is a rate-limiting step for the hormone response. In contrast, sgk does not appear to be the rate-limiting step for the cellular response to aldosterone or insulin.
引用
收藏
页码:C494 / C500
页数:7
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