Role of SGK in mineralocorticoid-regulated sodium transport

Mineralocorticoids stimulate electrogenic Na+ transport in tight epithelia by altering the transcription of specific genes. Although the earliest mine ralocorticoid effect is to increase the activity of the epithelial sodium c hannel (ENaC), ENaC mRNA and protein levels do not change. Instead, physiol ogic observations suggest that a mineralocorticoid target gene(s) encodes a n ENaC regulator(s). To begin to identify and characterize mineralocorticoi d-regulated target genes, we used suppression-subtractive hybridization to generate a cDNA library from A6 cells, a stable cell line of Xenopus laevis of distal nephron origin. A serine-threonine kinase, SGK, was identified f rom this screen. Sequence comparison revealed that frog, rat, and human SGK are 92% identical and 96% similar at the amino acid level. SGK mRNA was co nfirmed by Northern blot to be strongly and rapidly corticosteroid stimulat ed in A6 cells. In situ hybridization revealed that SGK was strongly stimul ated by aldosterone in rat collecting duct but not proximal tubule cells. L ow levels of SGK were present in rat glomeruli, but SGK was unregulated in this structure. Finally, SGK stimulated ENaC activity approximately sevenfo ld when coexpressed in Xenopus laevis oocytes. These data suggest that SGK is an important mediator of aldosterone effects on Na+ transport in tight e pithelia. In view of the existence of SGK homologues in invertebrates, it i s interesting to speculate that SGK is an ancient kinase that was adapted t o the control of epithelial Na+ transport by early vertebrates as they made the transition from a marine to a freshwater environment.