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

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.
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
Nature
Date: Feb. 12, 1998
Download Curated Data For This Publication
11945
Switch View:
  • Interactions 3