The serine/threonine kinases SGK2 and SGK3 are potent stimulators of the epithelial Na+ channel α,β,γ-ENaC
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The serum- and glucocorticoid-inducible kinase 1 (SGK1) has been identified as a signalling molecule up-regulated by aldosterone, which stimulates the renal epithelial Na+ channel ENaC. It is therefore thought to participate in the antinatriuretic action of this hormone. More recently, two isoforms, SGK2 and SGK3, have been cloned. The present study was performed to establish whether SGK2 and SGK3 influence ENaC activity similarly to SGK1. Dual-electrode voltage-clamp experiments in Xenopus laevis oocytes expressing α,ß,γ-ENaC with or without SGK1, SGK2 or SGK3 revealed a stimulatory effect of all three kinases on the amiloride-sensitive current (I Na). To establish whether the SGK isoforms exert their effects through direct phosphorylation, we replaced the serine at the SGK consensus site of αENaC (αS622AENaC) by site-directed mutagenesis. αS622A,β,γ-ENaC was up-regulated similar to wild-type ENaC, suggesting that SGK isoforms do not act via direct phosphorylation of the transport proteins. In conclusion, SGK2 and SGK3 mimic the function of SGK1 and are likely to participate in the regulation of ENaC activity.
KeywordsSodium channel Sodium reabsorption ENaC Protein kinases Kidney
The authors are indebted to Dr. B. Rossier (Lausanne, Switzerland) for providing the ENaC constructs. They acknowledge the technical assistance of B. Noll and the meticulous preparation of the manuscript by Leijla Subasic. This study was supported by the Deutsche Forschungsgemeinschaft, Nr. La 315/4-4 and La 315/5-1, the Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie (Centre for Interdisciplinary Clinical Research) 01 KS 9602 (to FL) and the UK Medical Research Council and The Royal Society (to PC).
- 2.Blazer-Yost BL, Shah N, Jarred L, Cox M, Smith RM (1972) Insulin and IGF1 receptors in a model renal epithelium: receptor localization and characterization. Biochem Int 28:143–153Google Scholar
- 10.Lang F, Klingel K, Wagner CA, Stegen C, Wärntges S, Friedrich B, Lanzendörfer M, Melzig J, Moschen I, Steuer S, Waldegger S, Sauter M, Paulmichl M, Gerke V, Risler T, Gamba G, Capasso G, Kandolf R, Hebert SC, Massry SG, Bröer S (2000) Deranged transcriptional regulation of cell volume sensitive kinase hSGK in diabetic nephropathy. Proc Natl Acad Sci USA 97:8157–8162PubMedGoogle Scholar
- 13.Shigaev A, Asher C, Latter H, Garty H, Reuveny E (2000) Regulation of sgk by aldosterone and its effects on the epithelial Na+ channel. Am J Physiol 278:F613–F619Google Scholar