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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2008-8-26
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pubmed:abstractText |
Signal transduction by transforming growth factor beta (TGFbeta) coordinates physiological responses in diverse cell types. TGFbeta signals via type I and type II receptor serine/threonine kinases and intracellular Smad proteins that regulate transcription. Strength and duration of TGFbeta signaling is largely dependent on a negative-feedback program initiated during signal progression. We have identified an inducible gene target of TGFbeta/Smad signaling, the salt-inducible kinase (SIK), which negatively regulates signaling together with Smad7. SIK and Smad7 form a complex and cooperate to down-regulate the activated type I receptor ALK5. We further show that both the kinase and ubiquitin-associated domain of SIK are required for proper ALK5 degradation, with ubiquitin functioning to enhance SIK-mediated receptor degradation. Loss of endogenous SIK results in enhanced gene responses of the fibrotic and cytostatic programs of TGFbeta. We thus identify in SIK a negative regulator that controls TGFbeta receptor turnover and physiological signaling.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-11832225,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-11864992,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-11910072,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-12717440,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-12829707,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-14693422,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-15121845,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-15817471,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-15840165,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-16212511,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-16306228,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-16396636,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-16756488,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-17317136,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-17325209,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-7693660,
http://linkedlifedata.com/resource/pubmed/commentcorrection/18725536-7893599
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1540-8140
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
25
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pubmed:volume |
182
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
655-62
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pubmed:dateRevised |
2011-11-1
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pubmed:meshHeading |
pubmed-meshheading:18725536-Animals,
pubmed-meshheading:18725536-Cell Line,
pubmed-meshheading:18725536-Down-Regulation,
pubmed-meshheading:18725536-Enzyme Activation,
pubmed-meshheading:18725536-Enzyme Induction,
pubmed-meshheading:18725536-Humans,
pubmed-meshheading:18725536-Protein Binding,
pubmed-meshheading:18725536-Protein Structure, Tertiary,
pubmed-meshheading:18725536-Protein-Serine-Threonine Kinases,
pubmed-meshheading:18725536-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:18725536-Signal Transduction,
pubmed-meshheading:18725536-Smad7 Protein,
pubmed-meshheading:18725536-Transforming Growth Factor beta,
pubmed-meshheading:18725536-Ubiquitin
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pubmed:year |
2008
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pubmed:articleTitle |
TGFbeta induces SIK to negatively regulate type I receptor kinase signaling.
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pubmed:affiliation |
Ludwig Institute for Cancer Research, Uppsala University, Box 595 Biomedical Center, Uppsala, Sweden.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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