MyD88: An adapter that recruits IRAK to the IL-1 receptor complex
MyD88: An adapter that recruits IRAK to the IL-1 receptor complex
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DOI：
10.1016/s1074-7613(00)80402-1
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发表时间：
1997-12-01
期刊：
影响因子：
32.4
通讯作者：
Cao, ZD
中科院分区：
文献类型：
--
作者：
Wesche, H;Henzel, WJ;Cao, ZD
IL-1是一种促炎细胞因子，它通过两个不同跨膜链的受体复合体发出信号，产生多种细胞反应，包括激活转录因子NF-kappa B。在这里，我们展示了MyD88，一个功能未知的蛋白，在IL-L刺激后被招募到IL-L受体复合体中。MyD88既能与IL-L受体相关激酶IRAK结合，又能与两条受体链上的异源复合体(信号复合体)结合，从而介导IRAK与受体的结合。MyD88的C端与IL-L受体相互作用，阻断IL-L诱导的核因子-kappaB的激活，但不能阻断肿瘤坏死因子的激活。因此，MyD88在IL-L信号转导中的作用与Tradd和Tube相同，分别在肿瘤坏死因子和Toll途径中发挥作用：它将丝氨酸/苏氨酸蛋白激酶偶联到受体复合体上。
IL-1 is a proinflammatory cytokine that signals through a receptor complex of two different transmembrane chains to generate multiple cellular responses, including activation of the transcription factor NF-kappa B. Here we show that MyD88, a previously described protein of unknown function, is recruited to the IL-l receptor complex following IL-l stimulation. MyD88 binds to both IRAK (IL-l receptor-associated kinase) and the heterocomplex (the signaling complex) of the two receptor chains and thereby mediates the association of IRAK with the receptor. Ectopic expression of MyD88 or its death domain-containing N-terminus activates NF-kappa B. The C-terminus of MyD88 interacts with the IL-l receptor and blocks NF-kappa B activation induced by IL-l, but not by TNF. Thus, MyD88 plays the same role in IL-l signaling as TRADD and Tube do in TNF and Toll pathways, respectively: it couples a serine/threonine protein kinase to the receptor complex.