Flores SY Loffing-Cueni D Kamynina E Daidié D Gerbex C Chabanel S Dudler J Loffing J Staub O 2005 Aldosterone plays a central role in Na+ homeostasis by controlling Na+ reabsorption in the aldosterone-sensitive distal nephron involving the epithelial Na+ channel (ENaC). Part of the effects of aldosterone is mediated by serum and glucocorticoid-induced kinase 1 (Sgk1), a Ser/Thr kinase whose expression is rapidly induced by aldosterone and that increases in heterologous expression systems ENaC cell surface abundance and activity. Previous work in Xenopus laevis oocytes suggested that Sgk1 phosphorylates specific residues (Ser212 and Ser328) on the ubiquitin-protein ligase Nedd4-2, an enzyme that directly interacts with ENaC and negatively controls channel density at the plasma membrane. It further indicated that phosphorylation of Nedd4-2 led to impairment of ENaC/Nedd4-2 interaction and consequently to more channels at the cell surface. These data suggested a novel mode of aldosterone-dependent action, yet this was not demonstrated formally in epithelial cells that physiologically express ENaC. Here it is shown, with the use of an anti-phospho-Ser328-mNedd4-2 antibody, that 2 to 6 h of aldosterone treatment induces an increase in Nedd4-2 phosphorylation, both in a mouse cortical collecting duct cell line (mpkCCDcl4) and in kidneys of adrenalectomized rats. This augmentation, which is accompanied by a raise in Sgk1 expression and transepithelial Na+ transport, is sensitive to phosphatidylinositol-3 kinase inhibition, as is Sgk1 phosphorylation and Na+ transport. Hence, these data provide evidence in cortical collecting duct cells in vitro and in vivo that Sgk1-dependent phosphorylation of Nedd4-2 is part of the aldosterone response. application/pdf https://sonar.ch/global/documents/277970 eng info:eu-repo/semantics/altIdentifier/doi/10.1681/ASN.2004100828 info:eu-repo/semantics/altIdentifier/pmid/15958725 info:eu-repo/semantics/openAccess Journal of the American Society of Nephrology : JASN. - 2005 Adenoviridae Aldosterone Animals Cell Line Cryopreservation DNA, Complementary Endosomal Sorting Complexes Required for Transport Immediate-Early Proteins Kidney Kidney Tubules, Collecting Mice Nedd4 Ubiquitin Protein Ligases Phosphatidylinositol 3-Kinases Phosphoinositide-3 Kinase Inhibitors Phosphoric Monoester Hydrolases Phosphorylation Plasmids Protein Binding Protein-Serine-Threonine Kinases Rats Retroviridae Sodium Time Factors Ubiquitin-Protein Ligases Xenopus Proteins Xenopus laevis Aldosterone-induced serum and glucocorticoid-induced kinase 1 expression is accompanied by Nedd4-2 phosphorylation and increased Na+ transport in cortical collecting duct cells. http://purl.org/coar/resource_type/c_6501