Source:http://linkedlifedata.com/resource/pubmed/id/18549800
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2008-6-13
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pubmed:abstractText |
Antigen-dependent T cell activation drives the formation of signaling microclusters containing the adaptor SLP-76. Costimulatory integrins regulate SLP-76 phosphorylation and could influence SLP-76 microclusters in the integrin-rich periphery of the immune synapse. We report that costimulation by the integrin VLA-4 (alpha4beta1) required SLP-76 domains implicated in microcluster assembly. Pro-adhesive ligands enlarged the contact and increased the number of SLP-76 microclusters regardless of their costimulatory potential. Costimulatory VLA-4 ligands also prevented the centralization of SLP-76, promoted microcluster persistence, prolonged lateral interactions between SLP-76 and its upstream kinase, ZAP-70, and retained SLP-76 in tyrosine-phosphorylated peripheral structures. SLP-76 centralization was driven by dynamic actin polymerization and was correlated with inward actin flows. VLA-4 ligation retarded these flows, even in the absence of SLP-76. These data suggest a widely applicable model of costimulation, in which integrins promote sustained signaling by attenuating cytoskeletal movements that drive the centralization and inactivation of SLP-76 microclusters.
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Actins,
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Integrin alpha4beta1,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/SLP-76 signal Transducing adaptor...,
http://linkedlifedata.com/resource/pubmed/chemical/ZAP-70 Protein-Tyrosine Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/ZAP70 protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1097-4180
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
28
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
810-21
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:18549800-Actins,
pubmed-meshheading:18549800-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:18549800-Humans,
pubmed-meshheading:18549800-Integrin alpha4beta1,
pubmed-meshheading:18549800-Jurkat Cells,
pubmed-meshheading:18549800-Lymphocyte Activation,
pubmed-meshheading:18549800-Phosphoproteins,
pubmed-meshheading:18549800-Signal Transduction,
pubmed-meshheading:18549800-T-Lymphocytes,
pubmed-meshheading:18549800-ZAP-70 Protein-Tyrosine Kinase
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pubmed:year |
2008
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pubmed:articleTitle |
T cell costimulation via the integrin VLA-4 inhibits the actin-dependent centralization of signaling microclusters containing the adaptor SLP-76.
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pubmed:affiliation |
Program in Immunology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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