Bruton's tyrosine kinase (Btk) - the critical tyrosine kinase in LPS signalling?
Bruton's tyrosine kinase (Btk) - the critical tyrosine kinase in LPS signalling?
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DOI：
10.1016/j.imlet.2003.11.017
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发表时间：
2004-03-29
影响因子：
4.4
通讯作者：
O'Neill, LAJ
中科院分区：
文献类型：
--
作者：
Jefferies, CA;O'Neill, LAJ
Toll 样受体 (TLR) 的发现彻底改变了先天免疫领域。关于 LPS 信号传导的一个未解决的问题是 LPS 受体下游的酪氨酸激酶是否发挥作用。先前对布鲁顿酪氨酸激酶缺陷小鼠的研究表明，它们对脂多糖的反应存在缺陷。对 Btk 在 LPS 信号传导中作用的进一步研究表明，Btk 直接涉及 TLR4 下游，无论是 p38 MAPK 激活还是转录因子 NFkappaB 激活。事实上，Btk 是由 LPS 激活的，并且已被证明可以直接结合 TLR4 和参与 LPS 诱导的 NFkappaB 激活的关键近端信号蛋白、MyD88、Mal 和 IRAK-1。这些最近的发现指出了 Btk 在 LPS 信号转导中的直接作用，并提出了有关 LPS 刺激后 Btk 激活模式以及 Btk 下游激活途径的精确性质的有趣问题。更好地了解 Btk 在 LPS 信号传导中的作用将对炎症和自身免疫性疾病及其治疗产生重要影响。 (C) 2003 Elsevier B.V. 保留所有权利。
The discovery of the Toll-like receptors (TLRs) has revolutionised the field of innate immunity. One unresolved question regarding LPS signalling is whether there is a role for tyrosine kinases downstream of the LPS receptor. Studies in mice deficient in Bruton's tyrosine kinase have previously shown that they are defective in their responses to LPS. Further investigation into the role of Btk in LPS signalling has directly implicated Btk downstream of TLR4, both with respect to p38 MAPK activation and activation of the transcription factor NFkappaB. In fact Btk is activated by LPS and has been shown to directly bind TLR4 and the key proximal signalling proteins involved in LPS-induced NFkappaB activation, MyD88, Mal and IRAK-1. These recent findings point to a direct role for Btk in LPS signal transduction and raise interesting questions regarding the mode of activation of Btk following LPS stimulation and the precise nature of the pathways activated downstream of Btk. A better understanding of how Btk functions in LPS signalling will have important implications for inflammatory and autoimmune disorders and therapies thereof. (C) 2003 Elsevier B.V. All rights reserved.