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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
1997-1-30
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pubmed:abstractText |
Recognition of major histocompatibility (MHC) class I complexes on target cells by killer cell inhibitory receptors (KIR) blocks natural killer (NK) and T cell cytotoxic function. The inhibitory effect of KIR ligation requires the phosphotyrosine-dependent association of KIR with the cytoplasmic SH2-containing protein tyrosine phosphatase SHP-1. Using a somatic genetic model, we first define a requirement for the Src family protein tyrosine kinase (PTK) Lck in mediating KIR tyrosine phosphorylation. We then investigate how KIR ligation interrupts PTK-dependent NK cell activation signals. Specifically, we show that KIR ligation inhibits the Fc receptor (FcR)-induced tyrosine phosphorylation of the FcR-associated zeta signaling chain, the PTK ZAP-70, and phospholipase C gamma. Overexpression of catalytically inactive SHP-1 (acting as a dominant negative) restores the tyrosine phosphorylation of these signaling events and reverses KIR-mediated inhibition of NK cell cytotoxic function. These results suggest sequential roles for Lck and SHP-1 in the inhibition of PTK following MHC recognition by NK cells.
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pubmed:grant |
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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/GEM protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Gem protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class I,
http://linkedlifedata.com/resource/pubmed/chemical/Immediate-Early Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Monomeric GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN6 protein, human,
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/Protein-Tyrosine Kinases,
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, Fc,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1074-7613
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
5
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
629-38
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8986721-Amino Acid Sequence,
pubmed-meshheading:8986721-Animals,
pubmed-meshheading:8986721-Cell Line,
pubmed-meshheading:8986721-Cytotoxicity, Immunologic,
pubmed-meshheading:8986721-GTP-Binding Proteins,
pubmed-meshheading:8986721-Histocompatibility Antigens Class I,
pubmed-meshheading:8986721-Humans,
pubmed-meshheading:8986721-Immediate-Early Proteins,
pubmed-meshheading:8986721-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:8986721-Killer Cells, Natural,
pubmed-meshheading:8986721-Major Histocompatibility Complex,
pubmed-meshheading:8986721-Mice,
pubmed-meshheading:8986721-Molecular Sequence Data,
pubmed-meshheading:8986721-Monomeric GTP-Binding Proteins,
pubmed-meshheading:8986721-Phosphorylation,
pubmed-meshheading:8986721-Protein Tyrosine Phosphatase, Non-Receptor Type 11,
pubmed-meshheading:8986721-Protein Tyrosine Phosphatase, Non-Receptor Type 6,
pubmed-meshheading:8986721-Protein Tyrosine Phosphatases,
pubmed-meshheading:8986721-Protein-Tyrosine Kinases,
pubmed-meshheading:8986721-Receptors, Fc,
pubmed-meshheading:8986721-Receptors, Immunologic,
pubmed-meshheading:8986721-Signal Transduction,
pubmed-meshheading:8986721-Tyrosine,
pubmed-meshheading:8986721-src-Family Kinases
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pubmed:year |
1996
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pubmed:articleTitle |
Sequential involvement of Lck and SHP-1 with MHC-recognizing receptors on NK cells inhibits FcR-initiated tyrosine kinase activation.
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pubmed:affiliation |
Department of Immunology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, 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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