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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.

Pubmed ID: 9490415


  • Lanier LL
  • Corliss BC
  • Wu J
  • Leong C
  • Phillips JH



Publication Data

February 12, 1998

Associated Grants


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