title: The serum and glucocorticoid kinase sgk increases the abundance of epithelial sodium channels in the plasma membrane of Xenopus oocytes.
abstract: The serum- and glucocorticoid-induced kinase (sgk) is a serine and threonine kinase that stimulates amiloride-sensitive sodium transport in Xenopus oocytes. Because aldosterone induces phosphorylation on serine/threonine (Ser/Thr) residues in the carboxyl termini of beta and gamma subunits of epithelial sodium channels (ENaCs) and causes an increase in the sgk transcript in mammalian and amphibian renal epithelial cells, it seems likely that sgk mediates the action of aldosterone to stimulate sodium transport. Experiments were performed in Xenopus oocytes to determine the mechanism by which sgk increases sodium conductance by examining its effect on phosphorylation, kinetics, and membrane abundance of ENaC. Our results demonstrate that deletions of the carboxyl termini of the three subunits do not inhibit sgk-induced sodium current, indicating that the effect of sgk is not mediated via phosphorylation within the carboxyl termini of ENaC. They also show no evidence that sgk reduces the removal of ENaC from the plasma membrane because mutations of tyrosine residues in the sequences necessary for endocytosis and degradation did not affect the response to sgk. Further studies performed with the patch-clamp technique indicated that sgk did not increase the open probability or changed the kinetics of ENaC. These studies, however, showed 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 increase in aldosterone-induced sodium current.
authors.affiliation: Department of Cellular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: D
authors.initials: D
authors.lastname: Alvarez de la Rosa
authors.forename: P
authors.initials: P
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Náray-Fejes-Tóth
authors.forename: G
authors.initials: G
authors.lastname: Fejes-Tóth
authors.forename: C M
authors.initials: CM
authors.lastname: Canessa
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D007700:Kinetics; D009687:Nuclear Proteins; D009865:Oocytes / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015222:Sodium Channels / Q000378:metabolism*; D013912:Threonine / Q000378:metabolism; D014982:Xenopus laevis; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011994:Recombinant Proteins; D012694:Serine; D015222:Sodium Channels; D013912:Threonine; D000099184:Serum-Glucocorticoid Regulated Kinases