Epithelial sodium channel regulated by aldosterone-induced protein sgk

Citation
Sy. Chen et al., Epithelial sodium channel regulated by aldosterone-induced protein sgk, P NAS US, 96(5), 1999, pp. 2514-2519
Citations number
47
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN journal
00278424 → ACNP
Volume
96
Issue
5
Year of publication
1999
Pages
2514 - 2519
Database
ISI
SICI code
0027-8424(19990302)96:5<2514:ESCRBA>2.0.ZU;2-4
Abstract
Sodium homeostasis in terrestrial and freshwater vertebrates is controlled by the corticosteroid hormones, principally aldosterone, which stimulate el ectrogenic Na+ absorption in tight epithelia. Although aldosterone is known to increase apical membrane Na+ permeability in target cells through chang es in gene transcription, the mechanistic basis of this effect remains poor ly understood. The predominant early effect of aldosterone is to increase t he activity of the epithelial sodium channel (ENaC), although ENaC mRNA and protein levels do not change initially. Rather, the open probability and/o r number of channels in the apical membrane are greatly increased by unknow n modulators. To identify hormone-stimulated gene products that modulate EN aC activity, a subtracted cDNA library was generated from A6 cells, a stabl e 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 ident ification of sgk (serum and glucocorticoid-regulated kinase), a member of t he serine-threonine kinase family as an aldosterone-induced regulator of EN aC activity. sgk mRNA and protein were strongly and rapidly hormone stimula ted both in A6 cells and in rat kidney. Furthermore, sgk stimulated ENaC ac tivity approximately 7-fold when they were coexpressed in Xenopus laevis oo cytes. These data suggest that sgk plays a central role in aldosterone regu lation of Na+ absorption and thus in the control of extracellular fluid vol ume, blood pressure, and sodium homeostasis.