Mechanisms of mineralocorticoid action: determinants of receptor specificity and actions of regulated gene products.
The mineralocorticoid receptor (MR) and its close cousin, the glucocorticoid receptor (GR), share considerable structural and functional similarity, including indistinguishable DNA binding properties, yet they mediate distinct physiological responses in some tissues. Specificity is determined by their distinct interactions with other protein factors and modification by peptides, including the small ubiquitin modifier SUMO1. Serum and glucocorticoid-regulated kinase 1 (sgk1) is one key target gene of both MR and GR, and encodes a serine-threonine kinase that stimulates the apical membrane localization of the epithelial sodium channel ENaC. Sgk1 exerts its effects, at least in part, by inhibiting an isoform of the ENaC inhibitory ubiquitin ligase Nedd4-2. This review briefly summarizes two areas of mineralocorticoid research: molecular determinants of MR specificity, and the role of Sgk1 in mediating the effects of aldosterone on epithelial Na(+) transport.
Bhargava
Aditi
A
Departments of Medicine and Cellular and Molecular Pharmacology, Box 2140, N272C Genentach Hall, University of California, San Francisco, CA 94143-2140, USA.
Pearce
David
D
D000818:Animals; D006801:Humans; D017874:Immediate-Early Proteins; D008901:Mineralocorticoids / Q000494:pharmacology*; D009687:Nuclear Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000494:pharmacology*; D018161:Receptors, Mineralocorticoid / Q000187:drug effects* / Q000235:genetics*; D000099184:Serum-Glucocorticoid Regulated Kinases
D017874:Immediate-Early Proteins; D008901:Mineralocorticoids; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011506:Proteins; D018161:Receptors, Mineralocorticoid; D000099184:Serum-Glucocorticoid Regulated Kinases