| pubmed-article:19917253 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:19917253 | lifeskim:mentions | umls-concept:C1334468 | lld:lifeskim |
| pubmed-article:19917253 | lifeskim:mentions | umls-concept:C0037083 | lld:lifeskim |
| pubmed-article:19917253 | lifeskim:mentions | umls-concept:C0023689 | lld:lifeskim |
| pubmed-article:19917253 | lifeskim:mentions | umls-concept:C0040690 | lld:lifeskim |
| pubmed-article:19917253 | lifeskim:mentions | umls-concept:C0041538 | lld:lifeskim |
| pubmed-article:19917253 | lifeskim:mentions | umls-concept:C1417660 | lld:lifeskim |
| pubmed-article:19917253 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
| pubmed-article:19917253 | lifeskim:mentions | umls-concept:C2349209 | lld:lifeskim |
| pubmed-article:19917253 | lifeskim:mentions | umls-concept:C1549649 | lld:lifeskim |
| pubmed-article:19917253 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:19917253 | lifeskim:mentions | umls-concept:C1521840 | lld:lifeskim |
| pubmed-article:19917253 | pubmed:issue | 3 | lld:pubmed |
| pubmed-article:19917253 | pubmed:dateCreated | 2009-11-17 | lld:pubmed |
| pubmed-article:19917253 | pubmed:abstractText | TGF-beta induces phosphorylation of the transcription factors Smad2 and Smad3 at the C terminus as well as at an interdomain linker region. TGF-beta-induced linker phosphorylation marks the activated Smad proteins for proteasome-mediated destruction. Here, we identify Nedd4L as the ubiquitin ligase responsible for this step. Through its WW domain, Nedd4L specifically recognizes a TGF-beta-induced phosphoThr-ProTyr motif in the linker region, resulting in Smad2/3 polyubiquitination and degradation. Nedd4L is not interchangeable with Smurf1, a ubiquitin ligase that targets BMP-activated, linker-phosphorylated Smad1. Nedd4L limits the half-life of TGF-beta-activated Smads and restricts the amplitude and duration of TGF-beta gene responses, and in mouse embryonic stem cells, it limits the induction of mesoendodermal fates by Smad2/3-activating factors. Hierarchical regulation is provided by SGK1, which phosphorylates Nedd4L to prevent binding of Smad2/3. Previously identified as a regulator of renal sodium channels, Nedd4L is shown here to play a broader role as a general modulator of Smad turnover during TGF-beta signal transduction. | lld:pubmed |
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| pubmed-article:19917253 | pubmed:language | eng | lld:pubmed |
| pubmed-article:19917253 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:19917253 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:19917253 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:19917253 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:19917253 | pubmed:month | Nov | lld:pubmed |
| pubmed-article:19917253 | pubmed:issn | 1097-4164 | lld:pubmed |
| pubmed-article:19917253 | pubmed:author | pubmed-author:MassaguéJoanJ | lld:pubmed |
| pubmed-article:19917253 | pubmed:author | pubmed-author:Erdjument-Bro... | lld:pubmed |
| pubmed-article:19917253 | pubmed:author | pubmed-author:TempstPaulP | lld:pubmed |
| pubmed-article:19917253 | pubmed:author | pubmed-author:MaciasMaria... | lld:pubmed |
| pubmed-article:19917253 | pubmed:author | pubmed-author:SapkotaGopalG | lld:pubmed |
| pubmed-article:19917253 | pubmed:author | pubmed-author:AlarcónClaudi... | lld:pubmed |
| pubmed-article:19917253 | pubmed:author | pubmed-author:RahmanSadiaS | lld:pubmed |
| pubmed-article:19917253 | pubmed:author | pubmed-author:GaoShengS | lld:pubmed |
| pubmed-article:19917253 | pubmed:author | pubmed-author:ChenPan-YuPY | lld:pubmed |
| pubmed-article:19917253 | pubmed:author | pubmed-author:GoernerNinaN | lld:pubmed |
| pubmed-article:19917253 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:19917253 | pubmed:day | 13 | lld:pubmed |
| pubmed-article:19917253 | pubmed:volume | 36 | lld:pubmed |
| pubmed-article:19917253 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:19917253 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:19917253 | pubmed:pagination | 457-68 | lld:pubmed |
| pubmed-article:19917253 | pubmed:dateRevised | 2011-11-2 | lld:pubmed |
| pubmed-article:19917253 | pubmed:meshHeading | pubmed-meshheading:19917253... | lld:pubmed |
| pubmed-article:19917253 | pubmed:meshHeading | pubmed-meshheading:19917253... | lld:pubmed |
