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rdf:type |
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lifeskim:mentions |
umls-concept:C0020204,
umls-concept:C0033681,
umls-concept:C0039194,
umls-concept:C0079717,
umls-concept:C0600210,
umls-concept:C1269955,
umls-concept:C1314939,
umls-concept:C1421567,
umls-concept:C1527940,
umls-concept:C1705831,
umls-concept:C1710082,
umls-concept:C2347946,
umls-concept:C2699153
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pubmed:issue |
8
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pubmed:dateCreated |
1999-11-4
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pubmed:abstractText |
We previously showed that LFA-1-dependent in vitro invasion and in vivo migration of a T cell hybridoma was blocked in cells overexpressing a truncated dominant-negative zeta-associated protein (ZAP)-70. The truncated ZAP-70 also blocked LFA-1-dependent chemotaxis through ICAM-1-coated filters induced by 1 ng/ml stromal cell-derived factor-1, but not LFA-1-independent chemotaxis induced by 100 ng/ml stromal cell-derived factor-1. This suggested that LFA-1 engagement triggers a signal that amplifies a weak chemokine signal and that dominant-negative ZAP-70 blocks this LFA-1 signal. Here we show that cross-linking of part of the LFA-1 molecules with Abs causes activation of free LFA-1 molecules (not occupied by the Ab) on the same cell, which then bind to ICAM-2 on other cells. This causes cell aggregation that was also blocked by dominant-negative ZAP-70. Thus, an LFA-1 signal involving ZAP-70 activates other LFA-1 molecules, suggesting that the chemokine signal can be amplified by multiple cycles of LFA-1 activation. The chemokine and the LFA-1 signal were both blocked by a phospholipase C inhibitor and a calpain inhibitor, suggesting that one of the amplified signals is the phospholipase C-dependent activation of calpain. Finally, we show that both Src-homology 2 domains are required for inhibition of invasion, chemotaxis, and aggregation by the truncated ZAP-70, suggesting that ZAP-70 interacts with a phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) sequence. Remarkably, this is not an ITAM in the TCR/CD3 complex because this is not expressed by this T cell hybridoma.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3,3',4,5'-tetrahydroxystilbene,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Calpain,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Adhesion Molecules,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/ICAM2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin Fab Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphocyte Function-Associated...,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipase C gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Stilbenes,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases,
http://linkedlifedata.com/resource/pubmed/chemical/ZAP-70 Protein-Tyrosine Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Zap70 protein, mouse
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-1767
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
163
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4253-61
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:10510363-Animals,
pubmed-meshheading:10510363-Antibodies, Monoclonal,
pubmed-meshheading:10510363-Antigens, CD,
pubmed-meshheading:10510363-Binding Sites, Antibody,
pubmed-meshheading:10510363-Calpain,
pubmed-meshheading:10510363-Cell Adhesion,
pubmed-meshheading:10510363-Cell Adhesion Molecules,
pubmed-meshheading:10510363-Cell Aggregation,
pubmed-meshheading:10510363-Cell Movement,
pubmed-meshheading:10510363-Dose-Response Relationship, Immunologic,
pubmed-meshheading:10510363-Enzyme Inhibitors,
pubmed-meshheading:10510363-Hybridomas,
pubmed-meshheading:10510363-Immunoglobulin Fab Fragments,
pubmed-meshheading:10510363-Isoenzymes,
pubmed-meshheading:10510363-Lymphocyte Function-Associated Antigen-1,
pubmed-meshheading:10510363-Mice,
pubmed-meshheading:10510363-Peptide Fragments,
pubmed-meshheading:10510363-Phospholipase C gamma,
pubmed-meshheading:10510363-Protein-Tyrosine Kinases,
pubmed-meshheading:10510363-Rats,
pubmed-meshheading:10510363-Signal Transduction,
pubmed-meshheading:10510363-Stilbenes,
pubmed-meshheading:10510363-T-Lymphocytes,
pubmed-meshheading:10510363-Type C Phospholipases,
pubmed-meshheading:10510363-ZAP-70 Protein-Tyrosine Kinase
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pubmed:year |
1999
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pubmed:articleTitle |
LFA-1 to LFA-1 signals involve zeta-associated protein-70 (ZAP-70) tyrosine kinase: relevance for invasion and migration of a T cell hybridoma.
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pubmed:affiliation |
Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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