Dong Zhongjun, Cruz-Munoz Mario-Ernesto, Zhong Ming-Chao, Chen Riyan, Latour Sylvain, Veillette André
Laboratory of Molecular Oncology, Clinical Research Institute of Montréal, Montréal, Québec, Canada.
Nat Immunol. 2009 Sep;10(9):973-80. doi: 10.1038/ni.1763. Epub 2009 Aug 2.
The adaptors SAP, EAT-2 and ERT are specific to cells of the immune system and belong to the SAP family. All three are expressed in natural killer (NK) cells. Here we examined the global function of the SAP family using mice lacking SAP, EAT-2 and ERT. These adaptors acted together in a mechanism that was essential for the elimination of hematopoietic but not nonhematopoietic cells by NK cells. This function was mediated by many receptors of the SLAM family on NK cells that were engaged by ligands found solely on hematopoietic cells. In the absence of SAP-related adaptors, SLAM receptors lost their activating function and became inhibitory receptors that repressed other activating receptors, such as NKG2D. Hence, the SAP family is essential for the elimination of unwanted hematopoietic cells by NK cells.
衔接蛋白SAP、EAT-2和ERT是免疫系统细胞所特有的，属于SAP家族。这三种蛋白均在自然杀伤（NK）细胞中表达。在此，我们利用缺乏SAP、EAT-2和ERT的小鼠研究了SAP家族的整体功能。这些衔接蛋白通过一种机制共同发挥作用，该机制对于NK细胞清除造血细胞而非非造血细胞至关重要。此功能由NK细胞上许多信号淋巴细胞激活分子（SLAM）家族的受体介导，这些受体与仅在造血细胞上发现的配体结合。在缺乏与SAP相关的衔接蛋白时，SLAM受体失去其激活功能，变成抑制性受体，抑制其他激活受体，如NKG2D。因此，SAP家族对于NK细胞清除不需要的造血细胞至关重要。
