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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
14
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pubmed:dateCreated |
2000-8-10
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pubmed:abstractText |
Smad proteins are intracellular mediators of transforming growth factor beta (TGF-beta) and related cytokines and undergo ligand-induced nuclear translocation. Here we describe the identification of a nuclear localization signal (NLS) in the N-terminal region of Smad 3, the major Smad protein involved in TGF-beta signaling. An NLS-like basic motif (Lys(40)-Lys-Leu-Lys-Lys(44)), conserved among all pathway-specific Smad proteins, not only is responsible for constitutive nuclear localization of the isolated Smad 3 MH1 domain but also is crucial for Smad 3 nuclear import in response to ligand. Mutations in this motif completely abolished TGF-beta-induced nuclear translocation but had no impact on ligand-induced phosphorylation of Smad 3, complex formation with Smad 4, or specific binding to DNA. Hence Smad 3 proteins with NLS mutations are dominant-negative inhibitors of TGF-beta-induced transcriptional activation. Smad 4, which cannot translocate into the nucleus in the absence of Smad 3 or another pathway-specific Smad, contains a Glu in place of the last Lys in this motif. Smad 3 harboring the same mutation (K44E) does not undergo ligand-induced nuclear import. Conversely, the isolated Smad 4 MH1 domain does not accumulate in the nucleus but becomes nuclear enriched when Glu(49) is replaced with Lys. We propose that this highly conserved five-residue NLS motif determines ligand-induced nuclear translocation of all pathway-specific Smads.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-10559238,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-10611974,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-1547506,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-7774578,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-8653785,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-8756346,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-8777060,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-8878477,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-8893010,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-8980228,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-9214507,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-9380693,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-9384585,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-9389648,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-9393997,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-9660945,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-9716398,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-9741623,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-9759490,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-9759503,
http://linkedlifedata.com/resource/pubmed/commentcorrection/10884415-9765209
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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/Activin Receptors, Type I,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Localization Signals,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/Smad3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/TGF-beta type I receptor,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
97
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7853-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:10884415-Activin Receptors, Type I,
pubmed-meshheading:10884415-Amino Acid Sequence,
pubmed-meshheading:10884415-Binding Sites,
pubmed-meshheading:10884415-Biological Transport,
pubmed-meshheading:10884415-Cell Compartmentation,
pubmed-meshheading:10884415-Cell Nucleus,
pubmed-meshheading:10884415-DNA-Binding Proteins,
pubmed-meshheading:10884415-Molecular Sequence Data,
pubmed-meshheading:10884415-Nuclear Localization Signals,
pubmed-meshheading:10884415-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10884415-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:10884415-Signal Transduction,
pubmed-meshheading:10884415-Smad3 Protein,
pubmed-meshheading:10884415-Trans-Activators,
pubmed-meshheading:10884415-Transcriptional Activation,
pubmed-meshheading:10884415-Transforming Growth Factor beta
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pubmed:year |
2000
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pubmed:articleTitle |
A distinct nuclear localization signal in the N terminus of Smad 3 determines its ligand-induced nuclear translocation.
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pubmed:affiliation |
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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