A requirement for CARMA1 in TCR-induced NF-κB activation
A requirement for CARMA1 in TCR-induced NF-κB activation
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DOI：
10.1038/ni824
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发表时间：
2002-09-01
影响因子：
30.5
通讯作者：
Lin, X
中科院分区：
文献类型：
--
作者：
Wang, DH;You, Y;Lin, X
T细胞受体（TCR）复合物的刺激启动了多个信号级联反应，导致几个转录因子的激活，包括NF-kappaB家族成员。尽管人们已经深入研究了TCR的各种近端信号成分，但介导TCR诱导的NF-kappaB激活的远端成分在很大程度上仍然未知。利用体细胞诱变方法，我们克隆了一个carma1缺陷T细胞系。CARMA1（最初称为CARDII）的缺陷导致TCR诱导的NF-kappaB选择性活化受损，从而导致白细胞介素-2 （IL-2）产生缺陷。用CARMA1重组CARMA1缺陷细胞完全挽救了这一信号缺陷。综上所述，我们的研究结果表明，CARMA1是介导tcr诱导的NF-kappaB激活的重要信号成分。
Stimulation of the T cell receptor (TCR) complex initiates multiple signaling cascades that lead to the activation of several transcription factors, including the NF-kappaB family members. Although various proximal signaling components of the TCR have been intensively studied, the distal components that mediate TCR-induced NF-kappaB activation remain largely unknown. Using a somatic mutagenesis approach, we cloned a CARMA1-deficient T cell line. Deficiency in CARMA1 (originally known as CARDII) resulted in selectively impaired activation of NF-kappaB induced by the TCR and a consequent defect in interleukin-2 (IL-2) production. Reconstitution of the CARMA1-deficient cells with CARMA1 fully rescued this signaling defect. Together, our results show that CARMA1 is an essential signaling component that mediates TCR-induced NF-kappaB activation.