| http://purl.uniprot.org/citations/15576372 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15576372 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/15576372 | http://www.w3.org/2000/01/rdf-schema#comment | "Serum and glucocorticoid-regulated kinase (SGK) plays a key role in the regulation of epithelial Na+ transport. SGK phosphorylates Nedd4-2, an E3 ubiquitin-protein ligase that targets the epithelial Na+ channel (ENaC) for degradation. Phosphorylation increases Na+ transport by reducing Nedd4-2 binding to ENaC, which increases ENaC expression at the cell surface. Thus, SGK expression must be tightly controlled to maintain Na+ homeostasis. This occurs in part by regulation of SGK transcription; a variety of signals including steroid hormones (aldosterone and glucocorticoids) increase SGK levels by inducing transcription of SGK. However, SGK has a short half-life, suggesting that SGK levels might also be controlled by regulation of SGK degradation. Here we found that SGK degradation is mediated in part by Nedd4-2. Consistent with this model, overexpression of Nedd4-2 decreased steady-state levels of SGK in a dose-dependent manner by increasing SGK ubiquitination and degradation in the 26S proteasome. Conversely, silencing of Nedd4-2 by RNA interference stabilized SGK. Nedd4-2 phosphorylation potentiates SGK degradation; degradation was reduced by Nedd4-2 and SGK mutations that disrupt phosphorylation or by inhibition of SGK kinase activity. Together with previous work, the data support a model in which SGK and Nedd4-2 regulate one another in a reciprocal manner. SGK phosphorylates Nedd4-2, which reduces Nedd4-2 binding and inhibition of ENaC. Conversely, phosphorylation increases Nedd4-2-mediated degradation of SGK. Thus, by phosphorylating Nedd4-2, SGK induces its own degradation. This feedback inhibition may fine-tune the regulation of epithelial Na+ absorption."xsd:string |
| http://purl.uniprot.org/citations/15576372 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m411053200"xsd:string |
| http://purl.uniprot.org/citations/15576372 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m411053200"xsd:string |
| http://purl.uniprot.org/citations/15576372 | http://purl.uniprot.org/core/author | "Zhou R."xsd:string |
| http://purl.uniprot.org/citations/15576372 | http://purl.uniprot.org/core/author | "Zhou R."xsd:string |
| http://purl.uniprot.org/citations/15576372 | http://purl.uniprot.org/core/author | "Snyder P.M."xsd:string |
| http://purl.uniprot.org/citations/15576372 | http://purl.uniprot.org/core/author | "Snyder P.M."xsd:string |
| http://purl.uniprot.org/citations/15576372 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15576372 | http://purl.uniprot.org/core/date | "2005"xsd:gYear |
| http://purl.uniprot.org/citations/15576372 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/15576372 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/15576372 | http://purl.uniprot.org/core/pages | "4518-4523"xsd:string |
| http://purl.uniprot.org/citations/15576372 | http://purl.uniprot.org/core/pages | "4518-4523"xsd:string |
| http://purl.uniprot.org/citations/15576372 | http://purl.uniprot.org/core/title | "Nedd4-2 phosphorylation induces serum and glucocorticoid-regulated kinase (SGK) ubiquitination and degradation."xsd:string |
| http://purl.uniprot.org/citations/15576372 | http://purl.uniprot.org/core/title | "Nedd4-2 phosphorylation induces serum and glucocorticoid-regulated kinase (SGK) ubiquitination and degradation."xsd:string |
| http://purl.uniprot.org/citations/15576372 | http://purl.uniprot.org/core/volume | "280"xsd:string |
| http://purl.uniprot.org/citations/15576372 | http://purl.uniprot.org/core/volume | "280"xsd:string |
| http://purl.uniprot.org/citations/15576372 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15576372 |
| http://purl.uniprot.org/citations/15576372 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/15576372 |
| http://purl.uniprot.org/citations/15576372 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/15576372 |
| http://purl.uniprot.org/citations/15576372 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/15576372 |
| http://purl.uniprot.org/uniprot/O00141 | http://purl.uniprot.org/core/citation | http://purl.uniprot.org/citations/15576372 |
| http://purl.uniprot.org/uniprot/Q96PU5 | http://purl.uniprot.org/core/citation | http://purl.uniprot.org/citations/15576372 |