Source:http://linkedlifedata.com/resource/pubmed/id/20668219
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
|
| pubmed:dateCreated |
2010-8-20
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| pubmed:abstractText |
Signaling lymphocytic activation molecule-associated protein (SAP), an adaptor molecule that recruits Fyn to the signaling lymphocytic activation molecule (SLAM) family of immunomodulatory receptors, is mutated in X-linked lymphoproliferative disease. CD4(+) T cells from SAP-deficient mice have defective TCR-induced and follicular Th cell IL-4 production and impaired T cell-mediated help for germinal center formation; however, the downstream intermediates contributing to these defects remain unclear. We previously found that SAP-deficient CD4(+) T cells exhibit decreased protein kinase C (PKC)-theta recruitment upon TCR stimulation. We demonstrate in this paper using GST pulldowns and coimmunoprecipitation studies that SAP constitutively associates with PKC- in T cells. SAP-PKC-theta interactions required R78 of SAP, a residue previously implicated in Fyn recruitment, yet SAP's interactions with PKC-theta occurred independent of phosphotyrosine binding and Fyn. Overexpression of SAP in T cells increased and sustained PKC-theta recruitment to the immune synapse and elevated IL-4 production in response to TCR plus SLAM-mediated stimulation. Moreover, PKC-theta, like SAP, was required for SLAM-mediated increases in IL-4 production, and, conversely, membrane-targeted PKC-theta mutants rescued IL-4 expression in SAP(-/-) CD4(+) T cells, providing genetic evidence that PKC-theta is a critical component of SLAM/SAP-mediated pathways that influence TCR-driven IL-4 production.
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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/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/CD150 antigen,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-4,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Prkcq protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
|
| pubmed:issn |
1550-6606
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| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:day |
1
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| pubmed:volume |
185
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
2819-27
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| pubmed:meshHeading |
pubmed-meshheading:20668219-Animals,
pubmed-meshheading:20668219-Antigens, CD,
pubmed-meshheading:20668219-CD4-Positive T-Lymphocytes,
pubmed-meshheading:20668219-Cell Line,
pubmed-meshheading:20668219-Gene Expression Regulation,
pubmed-meshheading:20668219-Humans,
pubmed-meshheading:20668219-Interleukin-4,
pubmed-meshheading:20668219-Isoenzymes,
pubmed-meshheading:20668219-Jurkat Cells,
pubmed-meshheading:20668219-Lymphocyte Activation,
pubmed-meshheading:20668219-Mice,
pubmed-meshheading:20668219-Mice, Inbred C57BL,
pubmed-meshheading:20668219-Mice, Knockout,
pubmed-meshheading:20668219-Mice, Transgenic,
pubmed-meshheading:20668219-Protein Kinase C,
pubmed-meshheading:20668219-Protein Transport,
pubmed-meshheading:20668219-Receptors, Cell Surface,
pubmed-meshheading:20668219-Signal Transduction,
pubmed-meshheading:20668219-Up-Regulation
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| pubmed:year |
2010
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| pubmed:articleTitle |
Biochemical and genetic evidence for a SAP-PKC-theta interaction contributing to IL-4 regulation.
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| pubmed:affiliation |
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural,
Research Support, N.I.H., Intramural
|