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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2005-10-5
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pubmed:abstractText |
The SH2 domain containing leukocyte phosphoprotein of 76 kD (SLP-76) is critical for pre-TCR-mediated maturation to the CD4+CD8+ double positive (DP) stage in the thymus. The absolute block in SLP-76null mice at the CD4-CD8-CD44-CD25+ (double-negative 3, DN3) stage has hindered our understanding of the role of this adaptor in alphabeta TCR-mediated signal transduction in primary thymocytes and peripheral T lymphocytes. To evaluate the requirements for SLP-76 in these events, we used a cre-loxP approach to generate mice that conditionally delete SLP-76 after the DN3 checkpoint. These mice develop DP thymocytes that express the alphabeta TCR on the surface, but lack SLP-76 at the genomic DNA and protein levels. The DP compartment has reduced cellularity in young mice and fails to undergo positive selection to CD4+ or CD8+ single positive (SP) cells in vivo or activation-induced cell death in vitro. A small number of CD4+SP thymocytes are generated, but these cells fail to flux calcium in response to an alphabeta TCR-generated signal. Peripheral T cells are reduced in number, lack SLP-76 protein, and have an abnormal surface phenotype. These studies show for the first time that SLP-76 is required for signal transduction through the mature alphabeta TCR in primary cells of the T lineage.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-10523607,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-10746729,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-11067911,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-11728338,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-11869894,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-12070286,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-12496375,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-12555096,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-12614349,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-12810689,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-12932362,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-1359428,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-14722089,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-14770180,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-15661827,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-7630421,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-7706237,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-8409419,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-8483910,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-9275205,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-9324357,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-9665885,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-9695951,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-9780153,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16186188-9858516
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Oct
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pubmed:issn |
0022-1007
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
3
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pubmed:volume |
202
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
893-900
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:16186188-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:16186188-Animals,
pubmed-meshheading:16186188-Blotting, Southern,
pubmed-meshheading:16186188-Blotting, Western,
pubmed-meshheading:16186188-Calcium,
pubmed-meshheading:16186188-Cell Differentiation,
pubmed-meshheading:16186188-Cell Lineage,
pubmed-meshheading:16186188-Female,
pubmed-meshheading:16186188-Flow Cytometry,
pubmed-meshheading:16186188-Gene Deletion,
pubmed-meshheading:16186188-Mice,
pubmed-meshheading:16186188-Mice, Inbred C57BL,
pubmed-meshheading:16186188-Phosphoproteins,
pubmed-meshheading:16186188-Signal Transduction,
pubmed-meshheading:16186188-Stem Cells,
pubmed-meshheading:16186188-T-Lymphocyte Subsets,
pubmed-meshheading:16186188-Thymus Gland
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pubmed:year |
2005
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pubmed:articleTitle |
Conditional deletion reveals a cell-autonomous requirement of SLP-76 for thymocyte selection.
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pubmed:affiliation |
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, N.I.H., Extramural
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