rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2010-1-12
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pubmed:abstractText |
Lymphocyte integrins mediate cell arrest on endothelium during immune surveillance after activation by chemokine-stimulated inside-out signals. Here we show that a Vav1-talin complex in T cells is a key target for chemokine-triggered inside-out signaling leading to integrin alpha4beta1 activation. Thus, Vav1 dissociation from talin was required to generate high-affinity alpha4beta1 conformations. Assembly of the Vav1-talin complex required PtdIns(4,5)P(2), which was provided by talin-bound phosphatidylinositol phosphate kinase Igamma. Chemokine-promoted Vav1 dissociation from talin followed an initial increase in talin binding to alpha4beta1. This process was dependent on ZAP-70, which binds to and phosphorylates Vav1 in the complex, leading to further alpha4beta1 activation and cell adhesion strengthening. Moreover, Vav1-talin dissociation was needed for Rac1 activation, thus indicating that alpha4beta1 and Rac1 activation can be coupled by chemokine-stimulated ZAP-70 function. Our data suggest that Vav1 might function as a repressive adaptor of talin that must dissociate from alpha4beta1-talin complexes for efficient integrin activation.
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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/Chemokine CXCL12,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin alpha4beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-vav,
http://linkedlifedata.com/resource/pubmed/chemical/Talin,
http://linkedlifedata.com/resource/pubmed/chemical/VAV1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Cell Adhesion Molecule-1,
http://linkedlifedata.com/resource/pubmed/chemical/ZAP-70 Protein-Tyrosine Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/ZAP70 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/rac1 GTP-Binding Protein
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1097-4180
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pubmed:author |
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pubmed:copyrightInfo |
Copyright 2009 Elsevier Inc. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
18
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pubmed:volume |
31
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
953-64
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pubmed:meshHeading |
pubmed-meshheading:20005136-Cell Adhesion,
pubmed-meshheading:20005136-Cell Line, Tumor,
pubmed-meshheading:20005136-Cells, Cultured,
pubmed-meshheading:20005136-Chemokine CXCL12,
pubmed-meshheading:20005136-Humans,
pubmed-meshheading:20005136-Integrin alpha4beta1,
pubmed-meshheading:20005136-Phosphotransferases,
pubmed-meshheading:20005136-Proto-Oncogene Proteins c-vav,
pubmed-meshheading:20005136-RNA Interference,
pubmed-meshheading:20005136-Signal Transduction,
pubmed-meshheading:20005136-T-Lymphocytes,
pubmed-meshheading:20005136-Talin,
pubmed-meshheading:20005136-Transfection,
pubmed-meshheading:20005136-Vascular Cell Adhesion Molecule-1,
pubmed-meshheading:20005136-ZAP-70 Protein-Tyrosine Kinase,
pubmed-meshheading:20005136-rac1 GTP-Binding Protein
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pubmed:year |
2009
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pubmed:articleTitle |
Chemokine-induced Zap70 kinase-mediated dissociation of the Vav1-talin complex activates alpha4beta1 integrin for T cell adhesion.
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pubmed:affiliation |
Cellular and Molecular Medicine Program, Centro de Investigaciones Biológicas (CSIC), 28040 Madrid, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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