Source:http://linkedlifedata.com/resource/pubmed/id/16407299
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
11
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| pubmed:dateCreated |
2006-3-13
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| pubmed:abstractText |
Vinculin regulates both cell-cell and cell-matrix junctions and anchors adhesion complexes to the actin cytoskeleton through its interactions with the vinculin binding sites of alpha-actinin or talin. Activation of vinculin requires a severing of the intramolecular interactions between its N- and C-terminal domains, which is necessary for vinculin to bind to F-actin; yet how this occurs in cells is not resolved. We tested the hypothesis that talin and alpha-actinin activate vinculin through their vinculin binding sites. Indeed, we show that these vinculin binding sites have a high affinity for full-length vinculin, are sufficient to sever the head-tail interactions of vinculin, and they induce conformational changes that allow vinculin to bind to F-actin. Finally, microinjection of these vinculin binding sites specifically targets vinculin in cells, disrupting its interactions with talin and alpha-actinin and disassembling focal adhesions. In their native (inactive) states the vinculin binding sites of talin and alpha-actinin are buried within helical bundles present in their central rod domains. Collectively, these results support a model where the engagement of adhesion receptors first activates talin or alpha-actinin, by provoking structural changes that allow their vinculin binding sites to swing out, which are then sufficient to bind to and activate vinculin.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
17
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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 |
7228-36
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:16407299-Actinin,
pubmed-meshheading:16407299-Actins,
pubmed-meshheading:16407299-Animals,
pubmed-meshheading:16407299-Binding Sites,
pubmed-meshheading:16407299-Cell Adhesion,
pubmed-meshheading:16407299-Dose-Response Relationship, Drug,
pubmed-meshheading:16407299-Humans,
pubmed-meshheading:16407299-Kinetics,
pubmed-meshheading:16407299-Magnetic Resonance Spectroscopy,
pubmed-meshheading:16407299-Mice,
pubmed-meshheading:16407299-Mice, Transgenic,
pubmed-meshheading:16407299-Microscopy, Fluorescence,
pubmed-meshheading:16407299-Microscopy, Video,
pubmed-meshheading:16407299-Models, Biological,
pubmed-meshheading:16407299-Molecular Conformation,
pubmed-meshheading:16407299-NIH 3T3 Cells,
pubmed-meshheading:16407299-Protein Binding,
pubmed-meshheading:16407299-Protein Conformation,
pubmed-meshheading:16407299-Protein Structure, Secondary,
pubmed-meshheading:16407299-Protein Structure, Tertiary,
pubmed-meshheading:16407299-Surface Plasmon Resonance,
pubmed-meshheading:16407299-Talin,
pubmed-meshheading:16407299-Time Factors,
pubmed-meshheading:16407299-Vinculin
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| pubmed:year |
2006
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| pubmed:articleTitle |
The vinculin binding sites of talin and alpha-actinin are sufficient to activate vinculin.
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| pubmed:affiliation |
Department of Biochemistry, St. Jude Children's Research Hospital, 332 North Lauderdale Street, Memphis, TN 38105, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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