| pubmed-article:21852580 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:21852580 | lifeskim:mentions | umls-concept:C0022646 | lld:lifeskim |
| pubmed-article:21852580 | lifeskim:mentions | umls-concept:C0596019 | lld:lifeskim |
| pubmed-article:21852580 | lifeskim:mentions | umls-concept:C1417660 | lld:lifeskim |
| pubmed-article:21852580 | lifeskim:mentions | umls-concept:C1704259 | lld:lifeskim |
| pubmed-article:21852580 | lifeskim:mentions | umls-concept:C1705987 | lld:lifeskim |
| pubmed-article:21852580 | lifeskim:mentions | umls-concept:C0597484 | lld:lifeskim |
| pubmed-article:21852580 | lifeskim:mentions | umls-concept:C0598850 | lld:lifeskim |
| pubmed-article:21852580 | pubmed:issue | 9 | lld:pubmed |
| pubmed-article:21852580 | pubmed:dateCreated | 2011-9-1 | lld:pubmed |
| pubmed-article:21852580 | pubmed:abstractText | 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. | lld:pubmed |
| pubmed-article:21852580 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21852580 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21852580 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21852580 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21852580 | pubmed:language | eng | lld:pubmed |
| pubmed-article:21852580 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21852580 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:21852580 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21852580 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:21852580 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21852580 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:21852580 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:21852580 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:21852580 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:21852580 | pubmed:issn | 1533-3450 | lld:pubmed |
| pubmed-article:21852580 | pubmed:author | pubmed-author:GambaGerardoG | lld:pubmed |
| pubmed-article:21852580 | pubmed:author | pubmed-author:StokesJohn... | lld:pubmed |
| pubmed-article:21852580 | pubmed:author | pubmed-author:VázquezNormaN | lld:pubmed |
| pubmed-article:21852580 | pubmed:author | pubmed-author:KoestersRober... | lld:pubmed |
| pubmed-article:21852580 | pubmed:author | pubmed-author:StaubOlivierO | lld:pubmed |
| pubmed-article:21852580 | pubmed:author | pubmed-author:YangBaoliB | lld:pubmed |
| pubmed-article:21852580 | pubmed:author | pubmed-author:HooverRobert... | lld:pubmed |
| pubmed-article:21852580 | pubmed:author | pubmed-author:RonzaudCaroli... | lld:pubmed |
| pubmed-article:21852580 | pubmed:author | pubmed-author:Ruffieux-Daid... | lld:pubmed |
| pubmed-article:21852580 | pubmed:author | pubmed-author:LagnazDagmara... | lld:pubmed |
| pubmed-article:21852580 | pubmed:author | pubmed-author:MaBenjamin... | lld:pubmed |
| pubmed-article:21852580 | pubmed:author | pubmed-author:ArroyoJuan... | lld:pubmed |
| pubmed-article:21852580 | pubmed:author | pubmed-author:ModdesLaurenL | lld:pubmed |
| pubmed-article:21852580 | pubmed:author | pubmed-author:HauselPierret... | lld:pubmed |
| pubmed-article:21852580 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:21852580 | pubmed:volume | 22 | lld:pubmed |
| pubmed-article:21852580 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:21852580 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:21852580 | pubmed:pagination | 1707-19 | lld:pubmed |
| pubmed-article:21852580 | pubmed:dateRevised | 2011-11-2 | lld:pubmed |
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| pubmed-article:21852580 | pubmed:meshHeading | pubmed-meshheading:21852580... | lld:pubmed |
| pubmed-article:21852580 | pubmed:year | 2011 | lld:pubmed |
| pubmed-article:21852580 | pubmed:articleTitle | Nedd4-2 modulates renal Na+-Cl- cotransporter via the aldosterone-SGK1-Nedd4-2 pathway. | lld:pubmed |
| pubmed-article:21852580 | pubmed:affiliation | Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Instituto Mexico City, Mexico. | lld:pubmed |
| pubmed-article:21852580 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:21852580 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:21852580 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
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