Source:http://linkedlifedata.com/resource/pubmed/id/18802005
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
|
| pubmed:dateCreated |
2008-11-25
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| pubmed:abstractText |
We demonstrate that lck promoter-driven conditional expression of transgenic SPA-1, a Rap GTPase-activation protein, causes a profound defect of alphabeta T-cell development at the CD4/CD8 double-negative (DN) stage due to enhanced cell death without affecting gammadelta T-cell development. The effect was specific to the DN stage, because CD4 promoter-driven SPA-1 expression hardly affected T-cell development. Rap1A17, a dominant-negative Rap mutant, interfered with the generation of double-positive (DP) cells from Rag2(-/-) fetal thymocytes in vitro in the presence of anti-CD3epsilon antibody and Notch ligand. Rap GTPases were activated in a DN cell line by the expression of self-oligomerizing CD3 (CD8:CD3epsilon chimera), which substituted autonomous pre-T-cell receptor (TCR) signal, inducing CD69 expression and CD25 down-regulation. Reciprocally, expression of C3G, a Rap guanine nucleotide exchange factor, in both normal and Rag2(-/-) DN cells markedly enhanced Notch-dependent generation and expansion of DP cells without additional anti-CD3epsilon antibody, thus bypassing pre-TCR. Defective alphabeta T-cell development in the conditional SPA-1-transgenic mice was restored completely by introducing a p53(-/-) mutation. These results suggest that endogenous Rap GTPases downstream of pre-TCR play an essential role in rescuing pre-T cells from the p53-mediated checkpoint response, thus allowing Notch-mediated expansion and differentiation.
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| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GTPase-Activating Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Rag2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell...,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Notch,
http://linkedlifedata.com/resource/pubmed/chemical/Sipa1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/rap GTP-Binding Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
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| pubmed:issn |
1528-0020
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:day |
1
|
| pubmed:volume |
112
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
4565-73
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| pubmed:meshHeading |
pubmed-meshheading:18802005-Animals,
pubmed-meshheading:18802005-Cell Death,
pubmed-meshheading:18802005-Cell Differentiation,
pubmed-meshheading:18802005-Cell Proliferation,
pubmed-meshheading:18802005-DNA-Binding Proteins,
pubmed-meshheading:18802005-GTPase-Activating Proteins,
pubmed-meshheading:18802005-Gene Rearrangement, beta-Chain T-Cell Antigen Receptor,
pubmed-meshheading:18802005-Genes, p53,
pubmed-meshheading:18802005-Mice,
pubmed-meshheading:18802005-Mice, Inbred C57BL,
pubmed-meshheading:18802005-Mice, Transgenic,
pubmed-meshheading:18802005-Nuclear Proteins,
pubmed-meshheading:18802005-Receptors, Antigen, T-Cell, alpha-beta,
pubmed-meshheading:18802005-Receptors, Notch,
pubmed-meshheading:18802005-Signal Transduction,
pubmed-meshheading:18802005-T-Lymphocytes,
pubmed-meshheading:18802005-Thymus Gland,
pubmed-meshheading:18802005-rap GTP-Binding Proteins
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| pubmed:year |
2008
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| pubmed:articleTitle |
Essential role of Rap signal in pre-TCR-mediated beta-selection checkpoint in alphabeta T-cell development.
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| pubmed:affiliation |
Department of Immunology and Cell Biology, Kyoto University, Kyoto, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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