NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases
NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases
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DOI：
10.1038/ni930
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发表时间：
2003-06-01
影响因子：
30.5
通讯作者：
Colucci, F
中科院分区：
文献类型：
--
作者：
Zompi, S;Hamerman, JA;Colucci, F
在活化的小鼠自然杀伤（NK）细胞中，NKG 2D受体与两个细胞内衔接子DAP 10和DAP 12结合，分别触发磷脂酰肌醇3激酶（PI 3 K）和Syk家族蛋白酪氨酸激酶。在这里，我们表明，细胞毒性，而不是细胞因子的产生，是由NKG 2D在缺乏DAP 12或Syk家族成员Syk和ZAP 70的活化NK细胞中触发的。抑制PI 3 K可阻断这种细胞毒性，表明DAP 10-PI 3 K通路足以启动NKG 2D介导的靶细胞杀伤。我们的研究结果突出了NKG 2D效应器功能的信号传导差异，并表明受体及其衔接子之间的替代关联可能为单个受体提供双重“开启开关”，从而为小鼠NK细胞提供更多选择，通过这些选择触发细胞毒性。
In activated mouse natural killer (NK) cells, the NKG2D receptor associates with two intracellular adaptors, DAP10 and DAP12, which trigger phosphatidyl inositol 3 kinase (PI3K) and Syk family protein tyrosine kinases, respectively. Here we show that cytotoxicity, but not cytokine production, is triggered by NKG2D in activated NK cells lacking either DAP12 or the Syk family members Syk and ZAP70. Inhibition of PI3K blocks this cytotoxicity, suggesting that the DAP10-PI3K pathway is sufficient to initiate NKG2D-mediated killing of target cells. Our results highlight signaling divergence in the effector functions of NKG2D and indicate that alternative associations between a receptor and its adaptors may provide a single receptor with a dual 'on-switch', giving mouse NK cells more choices through which to trigger cytotoxicity.