HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/2/C492    most recent 00556.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Alvarez de la Rosa, D. Articles by Canessa, C. M. Search for Related Content PubMed PubMed Citation Articles by Alvarez de la Rosa, D. Articles by Canessa, C. M.

MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

SGK1 activates Na⁺-K⁺-ATPase in amphibian renal epithelial cells

¹Unidad de Farmacología, Facultad de Medicina, Universidad de La Laguna, La Laguna, Spain; ²Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut; and ³Departamento de Farmacología y Fisiología, Facultad de Medicina, Universidad de Zaragoza, Zaragoza, Spain

Submitted 7 November 2004 ; accepted in final form 22 September 2005

Serum- and glucocorticoid-induced kinase 1 (SGK1) is thought to be an important regulator of Na⁺ reabsorption in the kidney. It has been proposed that SGK1 mediates the effects of aldosterone on transepithelial Na⁺ transport. Previous studies have shown that SGK1 increases Na⁺ transport and epithelial Na⁺ channel (ENaC) activity in the apical membrane of renal epithelial cells. SGK1 has also been implicated in the modulation of Na⁺-K⁺-ATPase activity, the transporter responsible for basolateral Na⁺ efflux, although this observation has not been confirmed in renal epithelial cells. We examined Na⁺-K⁺-ATPase function in an A6 renal epithelial cell line that expresses SGK1 under the control of a tetracycline-inducible promoter. The results showed that expression of a constitutively active mutant of SGK1 (SGK1^T_S425D) increased the transport activity of Na⁺-K⁺-ATPase 2.5-fold. The increase in activity was a direct consequence of activation of the pump itself. The onset of Na⁺-K⁺-ATPase activation was observed between 6 and 24 h after induction of SGK1 expression, a delay that is significantly longer than that required for activation of ENaC in the same cell line (1 h). SGK1 and aldosterone stimulated the Na⁺ pump synergistically, indicating that the pathways mediated by these molecules operate independently. This observation was confirmed by demonstrating that aldosterone, but not SGK1^T_S425D, induced an 2.5-fold increase in total protein and plasma membrane Na⁺-K⁺-ATPase ₁-subunit abundance. We conclude that aldosterone increases the abundance of Na⁺-K⁺-ATPase, whereas SGK1 may activate existing pumps in the membrane in response to chronic or slowly acting stimuli.

sodium transport; serum- and glucocorticoid-induced kinase; A6 cells; sodium pump

This article has been cited by other articles:

				T. Li, S. Koshy, and H. G. Folkesson IL-1{beta}-induced cortisol stimulates lung fluid absorption in fetal guinea pigs via SGK-mediated Nedd4-2 inhibition Am J Physiol Lung Cell Mol Physiol, March 1, 2009; 296(3): L527 - L533. [Abstract] [Full Text] [PDF]

				M. W. Musch, A. Lucioni, and E. B. Chang Aldosterone regulation of intestinal Na absorption involves SGK-mediated changes in NHE3 and Na+ pump activity Am J Physiol Gastrointest Liver Physiol, November 1, 2008; 295(5): G909 - G919. [Abstract] [Full Text] [PDF]

				N. Schliebe, R. Strotmann, K. Busse, D. Mitschke, H. Biebermann, L. Schomburg, J. Kohrle, J. Bar, H. Rompler, J. Wess, et al. V2 vasopressin receptor deficiency causes changes in expression and function of renal and hypothalamic components involved in electrolyte and water homeostasis Am J Physiol Renal Physiol, October 1, 2008; 295(4): F1177 - F1190. [Abstract] [Full Text] [PDF]