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

Serum- and glucocorticoid-induced kinase 1 (SGKI) 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 (SGK1S425DT) 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 SGK1S425DT, induced an ∼2.5-fold increase in total protein and plasma membrane Na+-K+-ATPase a α1-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. [ABSTRACT FROM AUTHOR]