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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2001-8-17
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pubmed:abstractText |
The molecular basis of X-linked lymphoproliferative (XLP) disease has been attributed to mutations in the signaling lymphocytic activation molecule-associated protein (SAP), an src homology 2 domain-containing intracellular signaling molecule known to interact with the lymphocyte-activating surface receptors signaling lymphocytic activation molecule and 2B4. To investigate the effect of SAP defects on TCR signal transduction, herpesvirus saimiri-immortalized CD4 Th cells from XLP patients and normal healthy individuals were examined for their response to TCR stimulation. CD4 T cells of XLP patients displayed elevated levels of tyrosine phosphorylation compared with CD4 T cells from healthy individuals. In addition, downstream serine/threonine kinases are constitutively active in CD4 T cells of XLP patients. In contrast, TCR-mediated activation of Akt, c-Jun-NH(2)-terminal kinases, and extracellular signal-regulated kinases in XLP CD4 T cells was transient and rapidly diminished when compared with that in control CD4 T cells. Consequently, XLP CD4 T cells exhibited severe defects in up-regulation of IL-2 and IFN-gamma cytokine production upon TCR stimulation and in MLRs. Finally, SAP specifically interacted with a 75-kDa tyrosine-phosphorylated protein upon TCR stimulation. These results demonstrate that CD4 T cells from XLP patients exhibit aberrant TCR signal transduction and that the defect in SAP function is likely responsible for this phenotype.
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pubmed:grant |
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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/Antigens, CD3,
http://linkedlifedata.com/resource/pubmed/chemical/CD3 antigen, zeta chain,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Protein v-cbl,
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/Retroviridae Proteins, Oncogenic,
http://linkedlifedata.com/resource/pubmed/chemical/SH2D1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
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 |
Sep
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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 |
1
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pubmed:volume |
167
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2657-65
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11509608-Antigens, CD3,
pubmed-meshheading:11509608-Base Sequence,
pubmed-meshheading:11509608-Carrier Proteins,
pubmed-meshheading:11509608-Cell Transformation, Viral,
pubmed-meshheading:11509608-Cells, Cultured,
pubmed-meshheading:11509608-Cytokines,
pubmed-meshheading:11509608-DNA Primers,
pubmed-meshheading:11509608-Herpesvirus 2, Saimiriine,
pubmed-meshheading:11509608-Herpesvirus 4, Human,
pubmed-meshheading:11509608-Humans,
pubmed-meshheading:11509608-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:11509608-Lymphoproliferative Disorders,
pubmed-meshheading:11509608-Mitogen-Activated Protein Kinases,
pubmed-meshheading:11509608-Mutation,
pubmed-meshheading:11509608-Oncogene Protein v-cbl,
pubmed-meshheading:11509608-Phosphorylation,
pubmed-meshheading:11509608-Protein-Tyrosine Kinases,
pubmed-meshheading:11509608-Receptors, Antigen, T-Cell,
pubmed-meshheading:11509608-Retroviridae Proteins, Oncogenic,
pubmed-meshheading:11509608-Signal Transduction,
pubmed-meshheading:11509608-T-Lymphocytes, Helper-Inducer,
pubmed-meshheading:11509608-Tyrosine,
pubmed-meshheading:11509608-ZAP-70 Protein-Tyrosine Kinase
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pubmed:year |
2001
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pubmed:articleTitle |
Abnormal T cell receptor signal transduction of CD4 Th cells in X-linked lymphoproliferative syndrome.
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pubmed:affiliation |
Department of Microbiology and Molecular Genetics, New England Regional Primate Research Center, Harvard Medical School, Southborough, MA 01772, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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