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Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells.

Nature | Feb 12, 1998

http://www.ncbi.nlm.nih.gov/pubmed/9490415

Natural killer (NK) cells express cell-surface receptors of the immunoglobulin and C-type lectin superfamilies that recognize major histocompatibility complex (MHC) class I peptides and inhibit NK-cell-mediated cytotoxicity. These inhibitory receptors possess ITIM sequences (for immunoreceptor tyrosine-based inhibitory motifs) in their cytoplasmic domains that recruit SH2-domain-containing protein tyrosine phosphatases, resulting in inactivation of NK cells. Certain isoforms of these NK-cell receptors lack ITIM sequences and it has been proposed that these 'non-inhibitory' receptors may activate, rather than inhibit, NK cells. Here we show that DAP12, a disulphide-bonded homodimer containing an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain, non-covalently associates with membrane glycoproteins of the killer-cell inhibitory receptor (KIR) family without an ITIM in their cytoplasmic domain. Crosslinking of KIR-DAP12 complexes results in cellular activation, as demonstrated by tyrosine phosphorylation of cellular proteins and upregulation of early-activation antigens. Phosphorylated DAP12 peptides bind ZAP-70 and Syk protein tyrosine kinases, suggesting that the activation pathway is similar to that of the T- and B-cell antigen receptors.

Pubmed ID: 9490415 RIS Download

Mesh terms: Amino Acid Sequence | Animals | B-Lymphocytes | Base Sequence | Binding Sites | Cell Line | Cell Membrane | Chromosomes, Human, Pair 19 | Consensus Sequence | Cross-Linking Reagents | Cytoplasm | DNA, Complementary | Humans | Jurkat Cells | Killer Cells, Natural | Lymphocyte Activation | Mice | Molecular Sequence Data | Protein-Tyrosine Kinases | Receptors, Antigen | Receptors, Immunologic | Receptors, KIR | T-Lymphocytes | Transfection | Tyrosine | ZAP-70 Protein-Tyrosine Kinase

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