Differential requirements for Vav proteins in DAP10- and ITAM-mediated NK cell cytotoxicity.
Differential requirements for Vav proteins in DAP10- and ITAM-mediated NK cell cytotoxicity.
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DOI：
10.1084/jem.20031847
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发表时间：
2004-09-20
期刊：
影响因子：
--
通讯作者：
Swat W
中科院分区：
文献类型：
--
作者：
Cella M;Fujikawa K;Tassi I;Kim S;Latinis K;Nishi S;Yokoyama W;Colonna M;Swat W
自然杀伤（NK）细胞表达多种激活受体，通过含有DAP 10或免疫受体酪氨酸激活基序的衔接子（包括DAP 12和FcRγ）启动信号级联。在下游信号介质中，鸟嘌呤核苷酸交换因子Vav 1在激活中起关键作用。然而，Vav 1是否只调节部分或全部NK细胞活化途径仍存在争议。另外两种Vav家族分子Vav 2和Vav 3也可能参与NK细胞活化。在这里，我们使用缺乏一种、两种或所有三种Vav蛋白的小鼠来检查这些交换因子中的每一种对NK细胞介导的细胞毒性的相对贡献。我们发现，Vav 1缺陷足以破坏DAP 10介导的细胞毒性，而Vav 2和Vav 3的缺乏严重损害FcRγ和DAP 12介导的细胞毒性。我们的研究结果提供的证据表明，这三个Vav蛋白的功能，特别是在不同的途径，触发NK细胞的细胞毒性。
Natural killer (NK) cells express multiple activating receptors that initiate signaling cascades through DAP10- or immunoreceptor tyrosine-based activation motif–containing adapters, including DAP12 and FcRγ. Among downstream signaling mediators, the guanine nucleotide exchange factor Vav1 carries out a key role in activation. However, whether Vav1 regulates only some or all NK cell–activating pathways is matter of debate. It is also possible that two other Vav family molecules, Vav2 and Vav3, are involved in NK cell activation. Here, we examine the relative contribution of each of these exchange factors to NK cell–mediated cytotoxicity using mice lacking one, two, or all three Vav proteins. We found that Vav1 deficiency is sufficient to disrupt DAP10-mediated cytotoxicity, whereas lack of Vav2 and Vav3 profoundly impairs FcRγ- and DAP12-mediated cytotoxicity. Our results provide evidence that these three Vav proteins function specifically in distinct pathways that trigger NK cell cytotoxicity.
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影响因子：
15.3
作者：
Fujikawa, K;Miletic, AV;Alt, FW;Faccio, R;Brown, T;Hoog, J;Fredericks, J;Nishi, S;Mildiner, S;Moores, SL;Brugge, J;Rosen, FS;Swat, W
通讯作者：
Swat, W
影响因子：
11.4
作者：
Doody, GM;Billadeau, DD;Turner, M
通讯作者：
Turner, M
影响因子：
15.3
作者：
Riteau, B;Barber, DF;Long, EO
通讯作者：
Long, EO
影响因子：
30.5
作者：
Zompi, S;Hamerman, JA;Colucci, F
通讯作者：
Colucci, F
DOI：
10.1084/jem.20011663
发表时间：
2002-05-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Reynolds LF;Smyth LA;Norton T;Freshney N;Downward J;Kioussis D;Tybulewicz VL
通讯作者：
Tybulewicz VL