PKC-θ is required for TCR-induced NF-κB activation in mature but not immature T lymphocytes
PKC-θ is required for TCR-induced NF-κB activation in mature but not immature T lymphocytes
复制标题
DOI：
10.1038/35006090
复制
发表时间：
2000-03-23
期刊：
影响因子：
64.8
通讯作者：
Littman, DR
中科院分区：
文献类型：
--
作者：
Sun, ZM;Arendt, CW;Littman, DR
T淋巴细胞与抗原呈递细胞的有效相互作用导致T细胞抗原受体（TCR）聚集，并将大的信号传导复合物募集到细胞-细胞接触部位（1，2）。导致细胞因子基因表达的后续信号转导需要激活丝氨酸/苏氨酸特异性蛋白激酶C（PKC）的多种同工酶中的一种或多种（3）。在T细胞中表达的几种PKC同工酶中，PKC-θ在快速募集至TCR聚集位点方面是独特的（4）。在这里，我们表明，PKC-θ是必不可少的TCR介导的T细胞活化，但在TCR依赖性胸腺细胞发育过程中被抑制。TCR启动的NF-κ B活化在PKC-θ（-/-）成熟T淋巴细胞中不存在，但在胸腺细胞中是完整的。在突变小鼠中，肿瘤坏死因子α和白细胞介素-1对NF-κ B的激活不受影响。尽管在T细胞系中的研究已经表明PKC-B调节JNK信号传导途径的活化（5，6），但是JNK的诱导在来自突变小鼠的T细胞中是正常的。这些结果表明，PKC-θ在一个独特的途径中发挥作用，该途径将TCR信号传导复合物与成熟T淋巴细胞中NF-κ B的活化联系起来。
Productive interaction of a T lymphocyte with an antigen-presenting cell results in the clustering of the T-cell antigen receptor (TCR) and the recruitment of a large signalling complex to the site of cell-cell contact(1,2). Subsequent signal transduction resulting in cytokine gene expression requires the activation of one or more of the multiple isoenzymes of serine/threonine-specific protein kinase C (PKC)(3). Among the several PKC isoenzymes expressed in T cells, PKC-theta is unique in being rapidly recruited to the site of TCR clustering(4). Here we show that PKC-theta is essential for TCR-mediated T-cell activation, but is dispensable during TCR-dependent thymocyte development. TCR-initiated NF-kappa B activation was absent from PKC-theta(-/-) mature T lymphocytes, but was intact in thymocytes. Activation of NF-kappa B by tumour-necrosis factor alpha and interleukin-1 was unaffected in the mutant mice. Although studies in T-cell lines had suggested that PKC-B regulates activation of the JNK signalling pathway(5,6), induction of JNK was normal in T cells from mutant mice. These results indicate that PKC-theta functions in a unique pathway that links the TCR signalling, complex to the activation of NF-kappa B in mature T lymphocytes.