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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
46
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pubmed:dateCreated |
2004-11-8
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pubmed:abstractText |
A T cell receptor (TCR) recognizes and responds to an antigenic peptide in the context of major histocompatibility complex-encoded molecules. This provokes T cells to produce interleukin-2 (IL-2) through extracellular signal-regulated kinase (ERK) activation. We investigated the roles of B-Raf in TCR-mediated IL-2 production coupled with ERK activation in the Jurkat human T cell line. We found that TCR cross-linking could induce up-regulation of both B-Raf and Raf-1 activities, but Raf-1 activity was decreased rapidly. On the other hand, TCR-stimulated kinase activity of B-Raf was sustained. Expression of a dominant-negative mutant of B-Raf abrogated sustained but not transient TCR-mediated MEK/ERK activation. The inhibition of sustained ERK activation by either expression of a dominant-negative B-Raf or treatment with a MEK inhibitor resulted in a decrease of the TCR-stimulated nuclear factor of activated T cells (NFAT) activity and IL-2 production. Collectively, our data provide the first direct evidence that B-Raf is a positive regulator of TCR-mediated sustained ERK activation, which is required for NFAT activation and the full production of IL-2.
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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/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/NFATC Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins B-raf,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
12
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
48457-65
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15339934-Animals,
pubmed-meshheading:15339934-Antigens, CD,
pubmed-meshheading:15339934-DNA-Binding Proteins,
pubmed-meshheading:15339934-Enzyme Activation,
pubmed-meshheading:15339934-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:15339934-Humans,
pubmed-meshheading:15339934-Interleukin-2,
pubmed-meshheading:15339934-Jurkat Cells,
pubmed-meshheading:15339934-MAP Kinase Kinase Kinases,
pubmed-meshheading:15339934-Mice,
pubmed-meshheading:15339934-NFATC Transcription Factors,
pubmed-meshheading:15339934-Nuclear Proteins,
pubmed-meshheading:15339934-Proto-Oncogene Proteins B-raf,
pubmed-meshheading:15339934-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:15339934-Receptors, Antigen, T-Cell,
pubmed-meshheading:15339934-Signal Transduction,
pubmed-meshheading:15339934-T-Lymphocytes,
pubmed-meshheading:15339934-Transcription Factor AP-1,
pubmed-meshheading:15339934-Transcription Factors
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pubmed:year |
2004
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pubmed:articleTitle |
B-Raf contributes to sustained extracellular signal-regulated kinase activation associated with interleukin-2 production stimulated through the T cell receptor.
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pubmed:affiliation |
Department of Immunogenetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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