sgk Is an Aldosterone-induced Kinase in the Renal Collecting Duct

TLDR

The early phase of aldosterone’s stimulatory effect on sodium reabsorption in renal epithelia involves activation of apical sodium channels, but the initiating genes are unknown. The study aimed to identify aldosterone‑regulated immediate early genes in renal mineralocorticoid target cells. We identified these genes by PCR‑based subtractive hybridization and differential display, and determined full‑length rabbit and mouse sgk cDNAs, which are highly homologous to rat and human sgk. Aldosterone rapidly increases sgk mRNA in cortical collecting duct cells within 30 min via mineralocorticoid receptors without new protein synthesis, and coexpression of sgk with ENaC subunits in Xenopus oocytes enhances Na⁺ current, indicating sgk mediates the early phase of aldosterone‑stimulated Na⁺ transport.

Abstract

The early phase of the stimulatory effect of aldosterone on sodium reabsorption in renal epithelia is thought to involve activation of apical sodium channels. However, the genes initiating this effect are unknown. We used a combination of polymerase chain reaction-based subtractive hybridization and differential display techniques to identify aldosterone-regulated immediate 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 cells, i.e. in cortical collecting duct cells. The effect occurs within 30 min of the addition of aldosterone, is mediated through mineralocorticoid receptors, and does not require de novo protein synthesis. The full-length sequences of rabbit and mouse sgk cDNAs were determined. Both cDNAs show significant 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 oocytes with the three subunits of the epithelial Na+ channel results in a significantly enhanced Na+ current. These results suggest that sgk is an immediate early aldosterone-induced gene, and this protein kinase plays an important role in the early phase of aldosterone-stimulated Na+ transport.