Background/Aim: Expression of the constitutively active form of serum and glucocorticoid-dependent kinase (S422DSGK1) in Xenopus oocytes has recently been shown to upregulate endogenous Na+/K+-ATPase activity, an effect presumably participating in the regulation of cellular K+ uptake and transepithelial Na+ transport. SGK1 and the two isoforms SGK2 and SGK3 are stimulated by insulin and insulin-like growth factor-1 (IGF-1), which have been shown to enhance Na+/K+-ATPase activity in a variety of cells. The present experiments have been performed to elucidate whether or not wild-type SGK1, SGK2 and SGK3 are similar to S422DSGK1 in being effective regulators of Na+/K+-ATPase. Methods: To this end, dual-electrode voltage clamp experiments were performed in Xenopus oocytes injected either with water or with mRNA of constitutively active S422DSGK1 and wild-type SGK1, SGK2 or SGK3. Na+/K+-ATPase activity was estimated from the outward-directed current created by readdition of extracellular K+ in the presence of K+ channel blocker Ba2+ following a 10-min exposure to K+-free extracellular fluid. Results: The outward-directed current was fully abolished by incubation with 1 mM ouabain and was significantly larger in oocytes expressing S422DSGK1, SGK1, SGK2 or SGK3, as compared to those injected with water. Conclusion: The stimulating effect of SGK1 on the Xenopus oocyte Na+/K+-ATPase is mimicked by the isoforms SGK2 and SGK3. Thus, all three kinases may participate in the regulation of Na+/K+-ATPase activity by hormones such as insulin and IGF-1.

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