Abstract
2B4 is a receptor belonging to the Ig superfamily and is found on all murine NK cells as well as a small subset of T cells. Previous studies have found that cross-linking of the 2B4 receptor results in both increased cytotoxicity and IFN-gamma secretion. We have discovered that 2B4 from transfected NK and T cell lines, as well as from primary murine cells, coimmunoprecipitates with the phosphoprotein linker for the activation of T cells (LAT), which is essential for TCR-mediated signaling. This association is independent of both 2B4 phosphorylation and the cytoplasmic tail of 2B4. We have found that, along with LAT, 2B4 is constitutively located in glycolipid-enriched microdomains of the plasma membrane. In fact, 2B4 appears to associate with LAT only when it localizes to glycolipid-enriched microdomains. This localization of 2B4 occurs due to a CxC cysteine motif found in the transmembrane region, as determined by mutagenesis studies. 2B4-mediated cytotoxicity is defective in the absence of LAT, indicating that LAT is a required intermediate for 2B4 signal transduction. However, we have also shown that LAT association alone is not sufficient for maximal 2B4 activation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Animals
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Antigens, CD*
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Carrier Proteins / metabolism*
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Carrier Proteins / physiology
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Cell Line
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Cytoplasm / genetics
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Cytoplasm / immunology
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Cytoplasm / metabolism
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Cytotoxicity, Immunologic* / genetics
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Glycolipids / metabolism*
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Humans
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Jurkat Cells
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism
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Lymphocyte Activation / immunology*
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Membrane Glycoproteins / chemistry
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / metabolism*
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Membrane Glycoproteins / physiology
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Membrane Microdomains / immunology*
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Membrane Microdomains / metabolism
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Membrane Proteins*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, SCID
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Mutagenesis, Site-Directed
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Phosphoproteins / metabolism*
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Phosphoproteins / physiology
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Phosphorylation
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Protein Isoforms / metabolism
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Protein Structure, Tertiary / genetics
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Receptors, Immunologic / chemistry
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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism*
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Receptors, Immunologic / physiology
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Signaling Lymphocytic Activation Molecule Family
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T-Lymphocytes* / immunology*
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T-Lymphocytes* / metabolism
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Transfection
Substances
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Adaptor Proteins, Signal Transducing
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Antigens, CD
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CD244 protein, human
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Carrier Proteins
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Cd244a protein, mouse
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Glycolipids
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LAT protein, human
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Lat protein, mouse
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Membrane Glycoproteins
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Membrane Proteins
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Phosphoproteins
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Protein Isoforms
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Receptors, Immunologic
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Signaling Lymphocytic Activation Molecule Family