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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2006-4-19
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pubmed:abstractText |
NKG2D is an important immunosurveillance receptor that responds to stress-induced ligand expression on tumors and virus-infected cells. Human natural killer cells express NKG2D and require the transmembrane adaptor DAP10 to initiate their full cytotoxic activation. However, DAP10 has no immunoreceptor tyrosine-based activation motif and thus the mechanism of recruiting 'downstream' effector proteins is unclear. We show here that binding of the p85 subunit of phosphatidylinositol-3- kinase to DAP10 could not by itself trigger cell-mediated cytotoxicity and that binding of an intermediate consisting of the DAP10 binding partner Grb2 and the effector molecule Vav1 (Grb2-Vav1) to DAP10 was sufficient to initiate tyrosine-phosphorylation events. For full calcium release and cytotoxicity to occur, both Grb2-Vav1 and p85 had to bind to DAP10. These findings identify a previously unknown mechanism by which NKG2D-DAP10 mediates cytotoxicity and provides a framework for evaluating activation by other receptor complexes that lack immunoreceptor tyrosine-based activation motifs.
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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/Antigens, Differentiation...,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/GNLY protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 Adaptor Protein,
http://linkedlifedata.com/resource/pubmed/chemical/GRB2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/HCST protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/KLRK1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NK Cell Lectin-Like Receptor...,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-vav,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Natural Killer Cell,
http://linkedlifedata.com/resource/pubmed/chemical/VAV1 protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1529-2908
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
7
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
524-32
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:16582911-Antigens, Differentiation, T-Lymphocyte,
pubmed-meshheading:16582911-Calcium,
pubmed-meshheading:16582911-Cell Line, Tumor,
pubmed-meshheading:16582911-Cytotoxicity, Immunologic,
pubmed-meshheading:16582911-GRB2 Adaptor Protein,
pubmed-meshheading:16582911-Humans,
pubmed-meshheading:16582911-Killer Cells, Natural,
pubmed-meshheading:16582911-Membrane Proteins,
pubmed-meshheading:16582911-Models, Biological,
pubmed-meshheading:16582911-NK Cell Lectin-Like Receptor Subfamily K,
pubmed-meshheading:16582911-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:16582911-Phosphorylation,
pubmed-meshheading:16582911-Proto-Oncogene Proteins c-vav,
pubmed-meshheading:16582911-Receptors, Immunologic,
pubmed-meshheading:16582911-Receptors, Natural Killer Cell,
pubmed-meshheading:16582911-Signal Transduction
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pubmed:year |
2006
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pubmed:articleTitle |
NKG2D-mediated signaling requires a DAP10-bound Grb2-Vav1 intermediate and phosphatidylinositol-3-kinase in human natural killer cells.
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pubmed:affiliation |
Department of Immunology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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