Source:http://linkedlifedata.com/resource/pubmed/id/15059847
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
2004-7-21
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pubmed:abstractText |
Engagement of the T-cell receptor (TCR) results in the activation of Lck/Fyn and ZAP-70/Syk tyrosine kinases. Lck-mediated tyrosine phosphorylation of signaling motifs (ITAMs) in the CD3-zeta subunits of the TCR is an initial step in the transduction of signaling cascades. However, zeta phosphorylation is also promoted by ZAP-70, as TCR-induced zeta phosphorylation is defective in ZAP-70-deficient T cells. We show that this defect is corrected by stable expression of ZAP-70, but not Syk, in primary and transformed T cells. Indeed, these proteins are differentially coupled to the TCR with a 5- to 10-fold higher association of ZAP-70 with zeta as compared to Syk. Low-level Syk-zeta binding is associated with significantly less Lck coupled to the TCR. Moreover, diminished coupling of Lck to zeta correlates with a poor phosphorylation of the positive regulatory tyr352 residue of Syk. Thus, recruitment of Lck into the TCR complex with subsequent zeta chain phosphorylation is promoted by ZAP-70 but not Syk. Importantly, the presence of ZAP-70 positively regulates the TCR-induced tyrosine phosphorylation of Syk. The interplay between Syk and ZAP-70 in thymocytes, certain T cells, and B-chronic lymphocytic leukemia cells, in which they are coexpressed, will therefore modulate the amplitude of antigen-mediated receptor signaling.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Subunits,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Syk kinase,
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/antigen T cell receptor, zeta chain
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0006-4971
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
104
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
760-7
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pubmed:dateRevised |
2011-11-2
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pubmed:meshHeading |
pubmed-meshheading:15059847-B-Lymphocytes,
pubmed-meshheading:15059847-Enzyme Precursors,
pubmed-meshheading:15059847-Humans,
pubmed-meshheading:15059847-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:15059847-Jurkat Cells,
pubmed-meshheading:15059847-Leukemia, Lymphocytic, Chronic, B-Cell,
pubmed-meshheading:15059847-Membrane Proteins,
pubmed-meshheading:15059847-Phosphorylation,
pubmed-meshheading:15059847-Protein Subunits,
pubmed-meshheading:15059847-Protein-Tyrosine Kinases,
pubmed-meshheading:15059847-Receptors, Antigen, T-Cell,
pubmed-meshheading:15059847-Signal Transduction,
pubmed-meshheading:15059847-T-Lymphocytes,
pubmed-meshheading:15059847-Thymus Gland,
pubmed-meshheading:15059847-ZAP-70 Protein-Tyrosine Kinase
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pubmed:year |
2004
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pubmed:articleTitle |
T-cell receptor-induced phosphorylation of the zeta chain is efficiently promoted by ZAP-70 but not Syk.
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pubmed:affiliation |
Institut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique Unité de Recherches 5535/Institut Fédératife de Recherche, F-34293 Montpellier 5, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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