sgk is an aldosterone-induced kinase in the renal collecting duct - Effects on epithelial Na+ channels

The early phase of the stimulatory effect of aldosterone on sodium reabsorp tion in renal epithelia is thought to involve activation of apical sodium c hannels. However, the genes initiating this effect are unknown. We used a c ombination of polymerase chain reaction-based subtractive hybridization and differential display techniques to identify aldosterone-regulated immediat e early genes in renal mineralocorticoid target cells. We report here that aldosterone rapidly increases mRNA levels of a putative Ser/Thr kinase, sgk (or serum- and glucocorticoid-regulated kinase), in its native target cell s, i.e. in cortical collecting duct cells. The effect occurs within 30 min of the addition of aldosterone, is mediated through mineralocorticoid recep tors, and does not require de novo protein synthesis. The full-length seque nces of rabbit and mouse sgk cDNAs were determined. Both cDNAs show signifi cant homology to rat and human sgk (88-94% at the nucleotide level, and 96- 99% at the amino acid level). Coexpression of the mouse sgk in Xenopus oocy tes with the three subunits of the epithelial Na+ channel results in a sign ificantly enhanced Na+ current. These results suggest that sgk is an immedi ate early aldosterone-induced gene, and this protein kinase plays an import ant role in the early phase of aldosterone-stimulated Na+ transport.