| First Author | Lanier LL | Year | 1998 |
| Journal | Nature | Volume | 391 |
| Issue | 6668 | Pages | 703-7 |
| PubMed ID | 9490415 | Mgi Jnum | J:49202 |
| Mgi Id | MGI:1276990 | Doi | 10.1038/35642 |
| Citation | Lanier LL, et al. (1998) Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells [see comments]. Nature 391(6668):703-7 |
| abstractText | 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 immuno-receptor 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. |
