DOI: 10.1073/pnas.96.5.2514. Epithelial sodium channel regulated by aldosterone-induced protein sgk

Epithelial sodium channel regulated by aldosterone-induced protein sgk

10.1073/pnas.96.5.2514

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

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 cells 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 plays a central role in aldosterone regulation of Na + absorption and thus in the control of extracellular fluid volume, blood pressure, and sodium homeostasis.

Bibliography

Chen, S., Bhargava, A., Mastroberardino, L., Meijer, O. C., Wang, J., Buse, P., Firestone, G. L., Verrey, F., & Pearce, D. (1999). Epithelial sodium channel regulated by aldosterone-induced protein sgk. Proceedings of the National Academy of Sciences, 96(5), 2514â2519.

Authors 9

Sei-yu Chen (first)
Aditi Bhargava (additional)
Luca Mastroberardino (additional)
Onno C. Meijer (additional)
Jian Wang (additional)
Patricia Buse (additional)
Gary L. Firestone (additional)
Francois Verrey (additional)
David Pearce (additional)

References 47 Referenced 596

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:35 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 5:36 p.m.)
Indexed	1 week, 1 day ago (Aug. 26, 2025, 2:53 a.m.)
Issued	26 years, 6 months ago (March 2, 1999)
Published	26 years, 6 months ago (March 2, 1999)
Published Online	26 years, 6 months ago (March 2, 1999)
Published Print	26 years, 6 months ago (March 2, 1999)

Funders 0

None

BibTeX

@article{Chen_1999, title={Epithelial sodium channel regulated by aldosterone-induced protein sgk}, volume={96}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.96.5.2514}, DOI={10.1073/pnas.96.5.2514}, number={5}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Chen, Sei-yu and Bhargava, Aditi and Mastroberardino, Luca and Meijer, Onno C. and Wang, Jian and Buse, Patricia and Firestone, Gary L. and Verrey, Francois and Pearce, David}, year={1999}, month=mar, pages={2514–2519} }

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    "1091-6490"
  ],
  "subject": [],
  "container-title-short": "Proc. Natl. Acad. Sci. U.S.A.",
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}