Campbell K S, Colonna M
Fox Chase Cancer Center, Institute for Cancer Research, Philadelphia, PA 19111, USA.
Int J Biochem Cell Biol. 1999 Jun;31(6):631-6. doi: 10.1016/s1357-2725(99)00022-9.
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.
DAP12是一种12 kDa的跨膜蛋白，最近被认为是自然杀伤（NK）细胞中的关键信号转导受体元件。它是一种通过二硫键连接的同型二聚体，与NK细胞上表达的几种激活受体非共价结合。预计通过DAP12启动的激活信号在触发NK细胞对某些肿瘤细胞和病毒感染细胞的细胞毒性反应中发挥关键作用。DAP12的胞质结构域包含一个基于免疫受体酪氨酸的激活基序（ITAM）。ITAM酪氨酸的磷酸化介导了与蛋白酪氨酸激酶的结合，这是T细胞和B细胞抗原受体中通过这些基序进行信号传导的一个显著特征。此外，它在包括树突状细胞和单核细胞在内的其他组织中的表达表明，DAP12也能为这些细胞中的一系列受体转导ITAM介导的激活信号。
