| Smad6 inhibits BMP/Smad1 signaling by specifically competing with the Smad4 tumor suppressor. | |
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MedLine Citation:
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PMID: 9436979 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Bone morphogenetic protein (BMP) receptors signal by phosphorylating Smad1, which then associates with Smad4; this complex moves into the nucleus and activates transcription. Here we report the existence of a natural inhibitor of this process, Smad6, a longer version of the previously reported JV15-1. In Xenopus embryos and in mammalian cells, Smad6 specifically blocks signaling by the BMP/Smad1 pathway. Smad6 inhibits BMP/Smad1 signaling without interfering with receptor-mediated phosphorylation of Smad1. Smad6 specifically competes with Smad4 for binding to receptor-activated Smad1, yielding an apparently inactive Smad1-Smad6 complex. Therefore, Smad6 selectively antagonizes BMP-activated Smad1 by acting as a Smad4 decoy. |
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Authors:
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A Hata; G Lagna; J Massagué; A Hemmati-Brivanlou |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Genes & development Volume: 12 ISSN: 0890-9369 ISO Abbreviation: Genes Dev. Publication Date: 1998 Jan |
Date Detail:
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Created Date: 1998-03-05 Completed Date: 1998-03-05 Revised Date: 2013-04-18 |
Medline Journal Info:
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Nlm Unique ID: 8711660 Medline TA: Genes Dev Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 186-97 Citation Subset: IM |
Affiliation:
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Cell Biology Program, Howard Hughes Medical Institute and The Sloan-Kettering Division of the Cornell University Graduate School of Medical Sciences, Memorial Sloan-Kettering Cancer Center, The Rockefeller University, New York, NY 10021, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Animals Bone Morphogenetic Protein Receptors Bone Morphogenetic Proteins / antagonists & inhibitors COS Cells Cells, Cultured DNA-Binding Proteins / antagonists & inhibitors*, genetics, physiology* Ectoderm / physiology Genes, Tumor Suppressor / physiology Humans Immunoblotting Molecular Sequence Data Receptors, Cell Surface / physiology Receptors, Growth Factor* Signal Transduction / genetics Smad Proteins Smad1 Protein Smad4 Protein Smad6 Protein Trans-Activators / physiology Transfection Xenopus Xenopus Proteins* |
| Grant Support | |
ID/Acronym/Agency:
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HD32105-01/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bone Morphogenetic Proteins; 0/DNA-Binding Proteins; 0/Receptors, Cell Surface; 0/Receptors, Growth Factor; 0/SMAD1 protein, human; 0/SMAD4 protein, human; 0/SMAD6 protein, human; 0/Smad Proteins; 0/Smad1 Protein; 0/Smad4 Protein; 0/Smad6 Protein; 0/Smad6 protein, Xenopus; 0/Trans-Activators; 0/Xenopus Proteins; 0/Xmad1 protein, Xenopus; 0/Xsmad4a protein, Xenopus; 0/Xsmad4b protein, Xenopus; EC 2.7.11.30/Bone Morphogenetic Protein Receptors |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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