| http://purl.uniprot.org/citations/21852580 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21852580 | http://www.w3.org/2000/01/rdf-schema#comment | "Regulation of renal Na(+) transport is essential for controlling blood pressure, as well as Na(+) and K(+) homeostasis. Aldosterone stimulates Na(+) reabsorption by the Na(+)-Cl(-) cotransporter (NCC) in the distal convoluted tubule (DCT) and by the epithelial Na(+) channel (ENaC) in the late DCT, connecting tubule, and collecting duct. Aldosterone increases ENaC expression by inhibiting the channel's ubiquitylation and degradation; aldosterone promotes serum-glucocorticoid-regulated kinase SGK1-mediated phosphorylation of the ubiquitin-protein ligase Nedd4-2 on serine 328, which prevents the Nedd4-2/ENaC interaction. It is important to note that aldosterone increases NCC protein expression by an unknown post-translational mechanism. Here, we present evidence that Nedd4-2 coimmunoprecipitated with NCC and stimulated NCC ubiquitylation at the surface of transfected HEK293 cells. In Xenopus laevis oocytes, coexpression of NCC with wild-type Nedd4-2, but not its catalytically inactive mutant, strongly decreased NCC activity and surface expression. SGK1 prevented this inhibition in a kinase-dependent manner. Furthermore, deficiency of Nedd4-2 in the renal tubules of mice and in cultured mDCT(15) cells upregulated NCC. In contrast to ENaC, Nedd4-2-mediated inhibition of NCC did not require the PY-like motif of NCC. Moreover, the mutation of Nedd4-2 at either serine 328 or 222 did not affect SGK1 action, and mutation at both sites enhanced Nedd4-2 activity and abolished SGK1-dependent inhibition. Taken together, these results suggest that aldosterone modulates NCC protein expression via a pathway involving SGK1 and Nedd4-2 and provides an explanation for the well-known aldosterone-induced increase in NCC protein expression."xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.org/dc/terms/identifier | "doi:10.1681/asn.2011020132"xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/author | "Yang B."xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/author | "Staub O."xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/author | "Koesters R."xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/author | "Gamba G."xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/author | "Vazquez N."xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/author | "Stokes J.B."xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/author | "Arroyo J.P."xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/author | "Hoover R.S."xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/author | "Lagnaz D."xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/author | "Ruffieux-Daidie D."xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/author | "Ko B.S."xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/author | "Hausel P."xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/author | "Ronzaud C."xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/author | "Moddes L."xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/name | "J Am Soc Nephrol"xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/pages | "1707-1719"xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/title | "Nedd4-2 modulates renal Na+-Cl- cotransporter via the aldosterone-SGK1-Nedd4-2 pathway."xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://purl.uniprot.org/core/volume | "22"xsd:string |
| http://purl.uniprot.org/citations/21852580 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21852580 |
| http://purl.uniprot.org/citations/21852580 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21852580 |
| http://purl.uniprot.org/uniprot/#_A0A494BAG2-mappedCitation-21852580 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21852580 |