| Chemokine-induced Zap70 kinase-mediated dissociation of the Vav1-talin complex activates alpha4beta1 integrin for T cell adhesion. | |
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MedLine Citation:
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PMID: 20005136 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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David Garc?a-Bernal; Marisa Parmo-Caba?as; Ana Dios-Esponera; Rafael Samaniego; Dolores Hern?n-P de la Ossa; Joaquin Teixid? |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-10 |
Journal Detail:
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Title: Immunity Volume: 31 ISSN: 1097-4180 ISO Abbreviation: Immunity Publication Date: 2009 Dec |
Date Detail:
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Created Date: 2010-01-12 Completed Date: 2010-02-09 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9432918 Medline TA: Immunity Country: United States |
Other Details:
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Languages: eng Pagination: 953-64 Citation Subset: IM |
Copyright Information:
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Copyright 2009 Elsevier Inc. All rights reserved. |
Affiliation:
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Cellular and Molecular Medicine Program, Centro de Investigaciones Biol?gicas (CSIC), 28040 Madrid, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Adhesion Cell Line, Tumor Cells, Cultured Chemokine CXCL12 / pharmacology Humans Integrin alpha4beta1 / metabolism* Phosphotransferases / metabolism Proto-Oncogene Proteins c-vav / drug effects, metabolism* RNA Interference Signal Transduction T-Lymphocytes / drug effects, immunology* Talin / drug effects, metabolism* Transfection Vascular Cell Adhesion Molecule-1 / metabolism ZAP-70 Protein-Tyrosine Kinase / metabolism* rac1 GTP-Binding Protein / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Chemokine CXCL12; 0/Integrin alpha4beta1; 0/Proto-Oncogene Proteins c-vav; 0/Talin; 0/VAV1 protein, human; 0/Vascular Cell Adhesion Molecule-1; EC 2.7.-/Phosphotransferases; EC 2.7.1.112/ZAP70 protein, human; EC 2.7.10.2/ZAP-70 Protein-Tyrosine Kinase; EC 3.6.5.2/rac1 GTP-Binding Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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