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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
25
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pubmed:dateCreated |
2006-6-19
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pubmed:abstractText |
Genetic evidence from both humans and mice suggests that Wnt/beta-catenin and bone morphogenetic protein (BMP) signaling pathways are essential for bone marrow mesenchymal stem cells to differentiate into osteoblasts. Here we describe a mechanism through which BMPs antagonize Wnt signaling and retard bone marrow mesenchymal stem cell proliferation. Treatment with Wnt3a, but not BMP-2, stimulated Lef1-mediated transcriptional activity, whereas co-stimulation with both Wnt3a and BMP-2 markedly reduced Wnt3a-induced reporter activity. Immunoprecipitation assays in 293T cells transfected with individual Smads and Wnt pathway components revealed a specific interaction between Dvl-1 and Smad1 that was dependent on the presence of Wnt3a or BMP-2. Under unstimulated conditions, Dvl-1 and Smad1 are co-immunoprecipitated and form a complex through the linker region of Smad1. Wnt3a treatment transiently disrupted the Dvl-1/Smad1 interaction coincident with nuclear accumulation of beta-catenin. In contrast, when cells were exposed to both Wnt3a and BMP-2, there was an enhanced accumulation of the Dvl-1-Smad1 complex and a decreased nuclear accumulation of beta-catenin. Expression of a mutant Smad1 protein, which cannot be phosphorylated in response to BMP, eliminated the inhibitory effect of BMP on Wnt-inducedbeta-catenin accumulation and transcriptional activity. These results identify a potential mechanism whereby BMP-2 antagonizes Wnt signaling in osteoblast progenitors by promoting an interaction between Smad1 and Dvl-1 that restricts beta-catenin activation.
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pubmed:grant |
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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/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/BMP2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bmp2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 2,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Smad1 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Smad1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/WNT3A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt3A Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt3a protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/dishevelled proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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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 |
23
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pubmed:volume |
281
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
17156-63
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:16621789-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:16621789-Animals,
pubmed-meshheading:16621789-Bone Marrow Cells,
pubmed-meshheading:16621789-Bone Morphogenetic Protein 2,
pubmed-meshheading:16621789-Bone Morphogenetic Proteins,
pubmed-meshheading:16621789-Humans,
pubmed-meshheading:16621789-Male,
pubmed-meshheading:16621789-Mice,
pubmed-meshheading:16621789-Mice, Inbred C57BL,
pubmed-meshheading:16621789-Phosphoproteins,
pubmed-meshheading:16621789-Signal Transduction,
pubmed-meshheading:16621789-Smad1 Protein,
pubmed-meshheading:16621789-Stromal Cells,
pubmed-meshheading:16621789-Transforming Growth Factor beta,
pubmed-meshheading:16621789-Wnt Proteins,
pubmed-meshheading:16621789-Wnt3 Protein,
pubmed-meshheading:16621789-Wnt3A Protein
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pubmed:year |
2006
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pubmed:articleTitle |
A dishevelled-1/Smad1 interaction couples WNT and bone morphogenetic protein signaling pathways in uncommitted bone marrow stromal cells.
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pubmed:affiliation |
Division of Molecular and Cellular Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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