DAP12: a key accessory protein for relaying signals by natural killer cell receptors.
DAP12 is a 12 kDa transmembrane protein recently recognized as a key signal transduction receptor element in Natural Killer (NK) cells. It is a disulfide-linked homodimer that non-covalently associates with several activating receptors expressed on NK cells. Activation signals initiated through DAP12 are predicted to play strategic roles in triggering NK cell cytotoxicity responses toward certain tumor cells and virally infected cells. The cytoplasmic domain of DAP12 contains an Immunoreceptor Tyrosine-based Activation Motif (ITAM). Phosphorylation of ITAM tyrosines mediates associations with protein tyrosine kinases, which is a resonant feature of signalling through these motifs in T and B cell antigen receptors. In addition, its expression in other tissues, including dendritic cells and monocytes, suggests that DAP12 transduces ITAM-mediated activation signals for an extended array of receptors in those cells as well.
Fox Chase Cancer Center, Institute for Cancer Research, Philadelphia, PA 19111, USA. ks_campbell@fccc.edu
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D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D011971:Receptors, Immunologic; C110546:TYROBP protein, human