Induction of the NF-κB cascade by recruitment of the scaffold molecule NEMO to the T cell receptor
Induction of the NF-κB cascade by recruitment of the scaffold molecule NEMO to the T cell receptor
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DOI：
10.1016/s1074-7613(02)00506-x
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发表时间：
2003-01-01
期刊：
影响因子：
32.4
通讯作者：
Israël, A
中科院分区：
文献类型：
--
作者：
Weil, R;Schwamborn, K;Israël, A
TCR信号激活核因子-kappaB的机制目前知之甚少。我们在这里证明，IKK激酶复合体被招募到免疫突触中，并在T细胞激活后与TCR共沉淀。利用表达ZAP-70 SH2结构域和Nemo/IKKGamma之间杂交分子的ZAP-70缺陷T细胞，我们证明了将Nemo靶向免疫突触，更具体地说，它的120个N末端氨基酸，足以选择性地恢复TCR连接后的NF-kappaB激活。最后，我们证明了NEMO靶向T细胞膜足以诱导组成性的核因子-kappaB激活。本研究表明，NEMO在免疫突触中的定位对TCR诱导的NF-kappaB活化具有重要意义，并为剖析T细胞中的NF-kappaB级联反应提供了一个强有力的系统。
The mechanism by which TCR signaling activates NF-kappaB is poorly understood. We demonstrate here that the IKK kinase complex is recruited to the immunological synapse and can be coprecipitated with the TCR after T cell activation. Using ZAP-70-deficient T cells expressing a hybrid molecule between the SH2 domain of ZAP-70 and NEMO/IKKgamma, we showed that targeting NEMO to the immunological synapse, and more specifically its 120 N-terminal amino acids, was sufficient to selectively restore NF-kappaB activation in response to TCR ligation. Finally, we demonstrated that targeting of NEMO to the membrane of T cells was sufficient to induce constitutive NF-kappaB activation. This study shows that the localization of NEMO to the immunological synapse is important for TCR-induced NF-kappaB activation and offers a powerful system to dissect the NF-kappaB cascade in T cells.