Am J Physiol Cell Physiol 2006 Feb 01;2902:C492-8. doi: 10.1152/ajpcell.00556.2004.

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

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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 approximately 2.5-fold increase in total protein and plasma membrane Na(+)-K(+)-ATPase alpha(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.

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Species referenced: Xenopus laevis
Genes referenced: sgk1