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首页> 外文期刊>Nature immunology >The kinase PDK1 integrates T cell antigen receptor and CD28 coreceptor signaling to induce NF-kappaB and activate T cells.
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The kinase PDK1 integrates T cell antigen receptor and CD28 coreceptor signaling to induce NF-kappaB and activate T cells.

机译:激酶PDK1整合了T细胞抗原受体和CD28核心受体信号,以诱导NF-κB和激活T细胞。

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摘要

In addition to ligation of the T cell antigen receptor (TCR), activation of the CD28 coreceptor by the costimulatory molecule B7 is required for induction of the transcription factor NF-kappaB and robust T cell activation, although the contribution of CD28 to this process remains incompletely understood. We show here that phosphoinositide-dependent kinase 1 (PDK1) is essential for integrating the TCR and CD28 signals. After we deleted PDK1 from T cells, TCR-CD28 signals were unable to induce activation of NF-kappaB or phosphorylation of protein kinase C-theta, although T cell survival and pathways dependent on the kinases p38 and Jnk or the transcription factor NFAT were unaffected. CD28 facilitated NF-kappaB activation by regulating recruitment and phosphorylation of PDK1, which are necessary for efficient binding of PDK1 to protein kinase C-theta and the adaptor CARMA1 and thus for NF-kappaB induction.
机译:除了连接T细胞抗原受体(TCR)以外,还需要通过共刺激分子B7激活CD28共受体,以诱导转录因子NF-κB和稳固的T细胞激活,尽管CD28对这一过程的贡献仍然存在不完全了解。我们在这里显示,磷酸肌醇依赖性激酶1(PDK1)对于整合TCR和CD28信号至关重要。从T细胞中删除PDK1之后,尽管T细胞存活和依赖于激酶p38和Jnk或转录因子NFAT的途径不受影响,但TCR-CD28信号无法诱导NF-κB的活化或蛋白激酶C-θ的磷酸化。 。 CD28通过调节PDK1的募集和磷酸化来促进NF-kappaB的活化,这对于PDK1与蛋白激酶C-θ和衔接子CARMA1的有效结合以及因此对NF-kappaB的诱导是必需的。

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