DAP12: a key accessory protein for relaying signals by Natural Killer cellreceptors

DAP12 is a 12 kDa transmembrane protein recently recognized as a key signal transduction receptor element in Natural Killer (NK) cells. It is a disulf ide-linked homodimer that non-covalently associates with several activating receptors expressed on NK cells, Activation signals initiated through DAP1 2 are predicted to play strategic roles in triggering NK cell cytotoxicity responses toward certain tumor cells and virally infected cells. The cytopl asmic 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 expressio n 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. (C) 1999 Elsevier Science Ltd. All rights reserved.