Functional specificity of Sgk1 and Akt1 on ENaC activity.
Reabsorption of sodium by the epithelial sodium channel (ENaC) is essential for maintaining the volume of the extracellular compartment and blood pressure. The function of ENaC is regulated primarily by aldosterone, antidiuretic hormone [arginine vasopressin (AVP)], and insulin, but the molecular mechanisms that increase channel activity are still poorly understood. It has been proposed that the related serine/threonine kinases serum- and glucocorticoid-induced kinase (Sgk1) and protein kinase B (Akt) mediate activation of ENaC. Here, we addressed the question of whether there is functional specificity of these kinases for the activation of ENaC in epithelial cells of the distal renal tubule. We demonstrate that Akt does not increase ENaC function under basal conditions or after stimulation with aldosterone, insulin, or AVP. In contrast, under the same experimental conditions, Sgk1 increases ENaC activity by 10-fold. The effect of Sgk1 is additive to that of aldosterone, whereas, in the presence of active Sgk1, cells do not further respond to insulin or AVP. We conclude that, in cells expressing both kinases, modulation of ENaC activity is mediated by Sgk1 but not by Akt1.
Arteaga
Maria Francisca
MF
Yale University School of Medicine, Dept. of Cellular and Molecular Physiology, New Haven, CT 06510, USA.
Canessa
Cecilia M
CM
D000818:Animals; D001127:Arginine Vasopressin / Q000502:physiology; D002460:Cell Line; D004847:Epithelial Cells / Q000502:physiology; D053503:Epithelial Sodium Channels; D005786:Gene Expression Regulation / Q000502:physiology*; D017874:Immediate-Early Proteins; D007328:Insulin / Q000502:physiology; D007668:Kidney / Q000166:cytology / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D015222:Sodium Channels / Q000502:physiology*; D013379:Substrate Specificity; D013752:Tetracycline; D000099184:Serum-Glucocorticoid Regulated Kinases
D001127:Arginine Vasopressin; D053503:Epithelial Sodium Channels; D017874:Immediate-Early Proteins; D007328:Insulin; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D015222:Sodium Channels; D013752:Tetracycline; D000099184:Serum-Glucocorticoid Regulated Kinases