Weil Robert, Schwamborn Klaus, Alcover Andrés, Bessia Christine, Di Bartolo Vincenzo, Israël Alain
Unité de Biologie Moléculaire de l'Expression Génique, FRE 2364 Centre National de la Recherche Scientifique (CNRS), 75724 Paris Cedex 15, France.
Immunity. 2003 Jan;18(1):13-26. doi: 10.1016/s1074-7613(02)00506-x.
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.
TCR信号激活NF-κB的机制目前还知之甚少。我们在此证明，IKK激酶复合物被招募到免疫突触，并且在T细胞活化后可与TCR共沉淀。使用表达ZAP-70的SH2结构域与NEMO/IKKγ之间的杂交分子的ZAP-70缺陷型T细胞，我们发现将NEMO靶向免疫突触，更具体地说是其120个N端氨基酸，足以选择性地恢复对TCR连接的NF-κB激活。最后，我们证明将NEMO靶向T细胞膜足以诱导组成型NF-κB激活。这项研究表明，NEMO在免疫突触中的定位对于TCR诱导的NF-κB激活很重要，并提供了一个强大的系统来剖析T细胞中的NF-κB级联反应。
