The serum and glucocorticoid-dependent kinase-1 (sgk1) is expressed in a wide variety of tissues including renal epithelial cells. As it is up-regulated by aldosterone, it is considered to participate in the regulation of renal Na(+) reabsorption. Indeed, co-expression of sgk1 with the renal epithelial Na(+) channel (ENaC) augments Na(+) channel activity. The aim of the present study was to examine possible effects of sgk1 on Na(+)/K(+)-ATPase activity. To this end dual-electrode voltage-clamp experiments were performed in Xenopus oocytes expressing the active kinase (S422D)sgk1 or the inactive mutant (K127N)sgk1. Na(+)/K(+)-ATPase activity was estimated from the hyperpolarization (delta V(m)) and the outwardly-directed current ( I(P)) created by addition of extracellular K(+) in the presence of K(+) channel blocker Ba(2+). Both delta V(m) and I(P) were significantly larger in oocytes expressing (S422D)sgk1 than in those expressing (K127N)sgk1 or having been injected with water. I(P) was fully inhibited by ouabain. Ion-selective microelectrodes showed that the stimulation of pump current was not the result of altered cytosolic Na(+) activity or pH. The present results thus point to an additional action of sgk1 that may participate in the regulation of renal tubular Na(+) transport. Moreover, sgk1 may be involved in the regulation of Na(+)/K(+)-ATPase in extrarenal tissues.