Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells - PubMed (original) (raw)
. 1998 Feb 12;391(6668):703-7.
doi: 10.1038/35642.
Affiliations
- PMID: 9490415
- DOI: 10.1038/35642
Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells
L L Lanier et al. Nature. 1998.
Abstract
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.
Comment in
- Immunology. Unmasking the killer's accomplice.
Colonna M. Colonna M. Nature. 1998 Feb 12;391(6668):642-3. doi: 10.1038/35515. Nature. 1998. PMID: 9490407 No abstract available.
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