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rdf:type |
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lifeskim:mentions |
umls-concept:C0022688,
umls-concept:C0024518,
umls-concept:C0162388,
umls-concept:C0205254,
umls-concept:C0205296,
umls-concept:C0221099,
umls-concept:C0376315,
umls-concept:C0456387,
umls-concept:C1335283,
umls-concept:C1521840,
umls-concept:C1705637
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pubmed:issue |
3
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pubmed:dateCreated |
2000-8-22
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pubmed:abstractText |
NK cell function is negatively regulated by MHC class I-specific inhibitory receptors. Transduction of the inhibitory signal involves protein tyrosine phosphatases such as SHP-1 (SH2-containing protein tyrosine phosphatase-1). To investigate the role of SHP-1 for NK cell development and function, we generated mice expressing a catalytically inactive, dominant-negative mutant of SHP-1 (dnSHP-1). In this paper we show that expression of dnSHP-1 does not affect the generation of NK cells even though MHC receptor-mediated inhibition is partially impaired. Despite this defect, these NK cells do not kill syngeneic, normal target cells. In fact dnSHP-1-expressing NK cells are hyporesponsive toward MHC-deficient target cells, suggesting that non-MHC-specific NK cell activation is significantly reduced. In contrast, these NK cells mediate Ab-dependent cell-mediated cytotoxicity and prevent the engraftment with beta2-microglobulin-deficient bone marrow cells. A similar NK cell phenotype is observed in viable motheaten (mev) mice, which show reduced SHP-1 activity due to a mutation in the Shp-1 gene. In addition, NK cells in both mouse strains show a tendency to express more inhibitory MHC-specific Ly49 receptors. Our results demonstrate the importance of SHP-1 for the generation of functional NK cells, which are able to react efficiently to the absence of MHC class I molecules from normal target cells. Therefore, SHP-1 may play an as-yet-unrecognized role in some NK cell activation pathways. Alternatively, a reduced capacity to transduce SHP-1-dependent inhibitory signals during NK cell development may be compensated by the down-modulation of NK cell triggering pathways.
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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, Ly,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Lectins, C-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Phosphatase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn11 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, NK Cell Lectin-Like,
http://linkedlifedata.com/resource/pubmed/chemical/SH2 Domain-Containing Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/beta 2-Microglobulin
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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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 |
165
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1314-21
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10903732-Animals,
pubmed-meshheading:10903732-Antigens, Ly,
pubmed-meshheading:10903732-Bone Marrow Transplantation,
pubmed-meshheading:10903732-Catalysis,
pubmed-meshheading:10903732-Cell Differentiation,
pubmed-meshheading:10903732-Cell Line,
pubmed-meshheading:10903732-Crosses, Genetic,
pubmed-meshheading:10903732-Cytotoxicity, Immunologic,
pubmed-meshheading:10903732-Enzyme Activation,
pubmed-meshheading:10903732-Graft Rejection,
pubmed-meshheading:10903732-Histocompatibility Antigens Class I,
pubmed-meshheading:10903732-Immunity, Innate,
pubmed-meshheading:10903732-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:10903732-Killer Cells, Natural,
pubmed-meshheading:10903732-Lectins, C-Type,
pubmed-meshheading:10903732-Membrane Glycoproteins,
pubmed-meshheading:10903732-Mice,
pubmed-meshheading:10903732-Mice, Mutant Strains,
pubmed-meshheading:10903732-Mice, Transgenic,
pubmed-meshheading:10903732-Mutagenesis, Insertional,
pubmed-meshheading:10903732-Point Mutation,
pubmed-meshheading:10903732-Protein Phosphatase 1,
pubmed-meshheading:10903732-Protein Tyrosine Phosphatase, Non-Receptor Type 11,
pubmed-meshheading:10903732-Protein Tyrosine Phosphatase, Non-Receptor Type 6,
pubmed-meshheading:10903732-Protein Tyrosine Phosphatases,
pubmed-meshheading:10903732-Receptors, NK Cell Lectin-Like,
pubmed-meshheading:10903732-SH2 Domain-Containing Protein Tyrosine Phosphatases,
pubmed-meshheading:10903732-T-Lymphocytes,
pubmed-meshheading:10903732-Tumor Cells, Cultured,
pubmed-meshheading:10903732-beta 2-Microglobulin,
pubmed-meshheading:10903732-src Homology Domains
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pubmed:year |
2000
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pubmed:articleTitle |
Impaired natural killing of MHC class I-deficient targets by NK cells expressing a catalytically inactive form of SHP-1.
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pubmed:affiliation |
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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