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首页> 外文期刊>Nature >PKC-θ is required for TCR-induced NF-κB activation in mature but not immature T lymphocytes
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PKC-θ is required for TCR-induced NF-κB activation in mature but not immature T lymphocytes

机译：TCR诱导成熟而非未成熟T淋巴细胞诱导NF-κB活化需要PKC-θ

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摘要

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. 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). Among the several PKC isoenzymes expressed in T cells, PKC-θ is unique in being rapidly recruited to the site of TCR clustering. Here we show that PKC-θ is essential for TCR-mediated T-cell activation, but is dispensable during TCR-depen-dent thymocyte development. TCR-initiated NF-κB activation was absent from PKC-θ~(-/-) mature T lymphocytes, but was intact in thymocytes. Activation of NF-κB by tumour-necrosis factor α and interleukin-1 was unaffected in the mutant mice. Although studies in T-cell lines had suggested that PKC-θ regulates activation of the JNK signalling pathway, induction of JNK was normal in T cells from mutant mice. These results indicate that PKC-θ functions in a unique pathway that links the TCR signalling complex to the activation of NF-κB in mature T lymphocytes.
机译：T淋巴细胞与抗原呈递细胞的生产性相互作用导致T细胞抗原受体（TCR）聚集，并且大信号复合物募集到细胞与细胞接触的部位。随后导致细胞因子基因表达的信号转导需要激活一种或多种丝氨酸/苏氨酸特异性蛋白激酶C（PKC）的多种同工酶。在T细胞中表达的几种PKC同工酶中，PKC-θ在迅速募集到TCR簇的位置方面是独特的。在这里，我们显示PKC-θ对于TCR介导的T细胞活化至关重要，但在TCR依赖的胸腺细胞发育过程中是必不可少的。 PKC-θ〜（-/-）成熟T淋巴细胞不存在TCR启动的NF-κB激活，但在胸腺细胞中却没有。在突变小鼠中，肿瘤坏死因子α和白介素-1对NF-κB的激活不受影响。尽管在T细胞系中的研究表明PKC-θ调节JNK信号通路的激活，但在突变小鼠的T细胞中JNK的诱导是正常的。这些结果表明，PKC-θ以独特的途径起作用，该途径将TCR信号复合物与成熟T淋巴细胞中的NF-κB的活化联系起来。

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