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rdf:type |
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lifeskim:mentions |
umls-concept:C0018270,
umls-concept:C0035820,
umls-concept:C0086982,
umls-concept:C0332120,
umls-concept:C0871261,
umls-concept:C1419746,
umls-concept:C1510411,
umls-concept:C1704632,
umls-concept:C1705633,
umls-concept:C1706817,
umls-concept:C2911692
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pubmed:issue |
29
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pubmed:dateCreated |
2004-7-12
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pubmed:abstractText |
Smad proteins are central mediators of the transforming growth factor-beta (TGF-beta) superfamily signaling. The mitogen-activated protein kinase (MAPK) p38 is also one of the downstream targets required for TGF-beta-mediated responses. Although the interplay between the p38 and Smad signaling pathways might allow cells to display diverse patterns of responses to TGF-beta, the mechanism of this cross-talk is not well established. We report here that inhibition of the p38alpha isoform suppressed the ability of Smad3 to mediate TGF-beta-induced transcriptional responses. The inhibition of p38 activity blocked TGF-beta-mediated phosphorylation of the MSK1 kinase, a substrate of p38 that plays an important role in the remodeling of chromatin. Moreover, we observed that expression of dominant-interfering mutants of MSK1 blocked the binding of Smad3 to the coactivator p300 in response to TGF-beta signaling. These data reveal a new mechanism whereby the Smad signaling pathway and the p38 cascade are integrated in the nucleus to activate gene expression.
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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 |
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Imidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 14,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Ribosomal Protein S6 Kinases, 90-kDa,
http://linkedlifedata.com/resource/pubmed/chemical/SB 203580,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Smad Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/mitogen and stress-activated...,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
30474-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15133024-Active Transport, Cell Nucleus,
pubmed-meshheading:15133024-Animals,
pubmed-meshheading:15133024-Blotting, Western,
pubmed-meshheading:15133024-COS Cells,
pubmed-meshheading:15133024-Cell Line, Tumor,
pubmed-meshheading:15133024-Chromatin,
pubmed-meshheading:15133024-DNA-Binding Proteins,
pubmed-meshheading:15133024-Enzyme Inhibitors,
pubmed-meshheading:15133024-Gene Expression Regulation,
pubmed-meshheading:15133024-Genes, Dominant,
pubmed-meshheading:15133024-Genes, Reporter,
pubmed-meshheading:15133024-Genetic Vectors,
pubmed-meshheading:15133024-Humans,
pubmed-meshheading:15133024-Imidazoles,
pubmed-meshheading:15133024-MAP Kinase Signaling System,
pubmed-meshheading:15133024-Microscopy, Confocal,
pubmed-meshheading:15133024-Mitogen-Activated Protein Kinase 14,
pubmed-meshheading:15133024-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15133024-Mutation,
pubmed-meshheading:15133024-Phosphorylation,
pubmed-meshheading:15133024-Plasmids,
pubmed-meshheading:15133024-Precipitin Tests,
pubmed-meshheading:15133024-Protein Binding,
pubmed-meshheading:15133024-Protein Isoforms,
pubmed-meshheading:15133024-Pyridines,
pubmed-meshheading:15133024-Recombinant Proteins,
pubmed-meshheading:15133024-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:15133024-Ribosomal Protein S6 Kinases, 90-kDa,
pubmed-meshheading:15133024-Signal Transduction,
pubmed-meshheading:15133024-Smad Proteins,
pubmed-meshheading:15133024-Smad3 Protein,
pubmed-meshheading:15133024-Time Factors,
pubmed-meshheading:15133024-Trans-Activators,
pubmed-meshheading:15133024-Transcription Factor AP-1,
pubmed-meshheading:15133024-Transfection,
pubmed-meshheading:15133024-Transforming Growth Factor beta,
pubmed-meshheading:15133024-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2004
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pubmed:articleTitle |
Evidence for a role of MSK1 in transforming growth factor-beta-mediated responses through p38alpha and Smad signaling pathways.
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pubmed:affiliation |
INSERM U542, Bâtiment Lavoisier, Hôpital Paul Brousse, 14 Avenue Paul Vaillant Couturier, 94807 Villejuif, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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