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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
12
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pubmed:dateCreated |
2001-11-28
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pubmed:abstractText |
The Tec kinases Rlk and Itk are critical for full T cell receptor (TCR)-induced activation of phospholipase C-gamma and mitogen-activated protein kinase. We show here that the mutation of Rlk and Itk impaired activation of the transcription factors NFAT and AP-1 and production of both T helper type 1 (TH1) and TH2 cytokines. Consistent with these biochemical defects, Itk-/- mice did not generate effective TH2 responses when challenged with Schistosoma mansoni eggs. Paradoxically, the more severely impaired Rlk-/-Itk-/- mice were able to mount a TH2 response and produced TH2 cytokines in response to this challenge. In addition, Rlk-/-Itk-/- cells showed impaired TCR-induced repression of the TH2-inducing transcription factor GATA-3, suggesting a potential mechanism for TH2 development in these hyporesponsive cells. Thus, mutations that affect Tec kinases lead to complex alterations in CD4+ TH cell differentiation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GATA3 Transcription Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Gata3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Immunoglobulin E,
http://linkedlifedata.com/resource/pubmed/chemical/NFATC Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Tec protein-tyrosine kinase,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/emt protein-tyrosine kinase
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1529-2908
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
2
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1183-8
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11702066-Animals,
pubmed-meshheading:11702066-Cell Differentiation,
pubmed-meshheading:11702066-Cells, Cultured,
pubmed-meshheading:11702066-Cytokines,
pubmed-meshheading:11702066-DNA-Binding Proteins,
pubmed-meshheading:11702066-GATA3 Transcription Factor,
pubmed-meshheading:11702066-Immunoglobulin E,
pubmed-meshheading:11702066-Lymphocyte Activation,
pubmed-meshheading:11702066-Mice,
pubmed-meshheading:11702066-Mice, Knockout,
pubmed-meshheading:11702066-Mutation,
pubmed-meshheading:11702066-NFATC Transcription Factors,
pubmed-meshheading:11702066-Nuclear Proteins,
pubmed-meshheading:11702066-Protein-Tyrosine Kinases,
pubmed-meshheading:11702066-RNA, Messenger,
pubmed-meshheading:11702066-Receptors, Antigen, T-Cell,
pubmed-meshheading:11702066-Schistosomiasis mansoni,
pubmed-meshheading:11702066-T-Lymphocytes, Helper-Inducer,
pubmed-meshheading:11702066-Th2 Cells,
pubmed-meshheading:11702066-Trans-Activators,
pubmed-meshheading:11702066-Transcription Factor AP-1,
pubmed-meshheading:11702066-Transcription Factors
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pubmed:year |
2001
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pubmed:articleTitle |
Mutation of Tec family kinases alters T helper cell differentiation.
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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, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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