Jefferies Caroline A, O'Neill Luke A J
Department of Biochemistry and Biotechnology Institute, Cytokine Research Group, Trinity College, Dublin 2, Ireland.
Immunol Lett. 2004 Mar 29;92(1-2):15-22. doi: 10.1016/j.imlet.2003.11.017.
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.
Toll样受体（TLR）的发现彻底改变了固有免疫领域。关于LPS信号传导，一个尚未解决的问题是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LPS的反应存在缺陷。对Btk在LPS信号传导中作用的进一步研究直接表明，Btk在TLR4下游发挥作用，这涉及p38 MAPK激活和转录因子NFκB的激活。事实上，Btk被LPS激活，并已被证明直接结合TLR4以及参与LPS诱导的NFκB激活的关键近端信号蛋白MyD88、Mal和IRAK-1。这些最新发现表明Btk在LPS信号转导中起直接作用，并引发了关于LPS刺激后Btk的激活模式以及Btk下游激活途径的确切性质的有趣问题。更好地理解Btk在LPS信号传导中的功能将对炎症和自身免疫性疾病及其治疗产生重要影响。
