The serum and glucocorticoid kinase sgk increases the abundance of epithelial sodium channels in the plasma membrane of Xenopus oocytes

The serum- and glucocorticoid-induced kinase (sgk) is a serine and threonin e kinase that stimulates amiloride-sensitive sodium transport in Xenopus oo cytes. Because aldosterone induces phosphorylation on serine/threonine (Ser /Thr) residues in the carboxyl termini of beta and gamma subunits of epithe lial sodium channels (ENaCs) and causes an increase in the sgk transcript i n mammalian and amphibian renal epithelial cells, it seems likely that sgk mediates the action of aldosterone to stimulate sodium transport. Experimen ts were performed in Xenopus oocytes to determine the mechanism by which sg k increases sodium conductance by examining its effect on phosphorylation, kinetics, and membrane abundance of ENaC. Our results demonstrate that dele tions of the carboxyl termini of the three subunits do not inhibit sgk-indu ced sodium current, indicating that the effect of sgk is not mediated via p hosphorylation within the carboxyl termini of ENaC. They also show no evide nce that sgk reduces the removal of ENaC from the plasma membrane because m utations of tyrosine residues in the sequences necessary for endocytosis an d degradation did not affect the response to sgk. Further studies performed with the patch-clamp technique indicated that sgk did not increase the ope n probability or changed the kinetics of ENaC. These studies, however, show ed a 3-fold increase in the abundance of ENaC in the plasma membrane in the presence of sgk compared with control. Together, the experiments indicate that sgk stimulates electrogenic sodium transport by increasing the number of ENaCs at the cell surface and suggest that sgk may mediate the early inc rease in aldosterone-induced sodium current.