髓样分化因子88（MyD88）：一种将白细胞介素-1受体相关激酶（IRAK）募集至白细胞介素-1受体复合物的衔接蛋白。

MyD88: an adapter that recruits IRAK to the IL-1 receptor complex.

作者信息

Wesche H, Henzel W J, Shillinglaw W, Li S, Cao Z

机构信息

Tularik, Incorporated, South San Francisco, California 94080, USA.

出版信息

Immunity. 1997 Dec;7(6):837-47. doi: 10.1016/s1074-7613(00)80402-1.

DOI:10.1016/s1074-7613(00)80402-1

PMID:9430229

Abstract

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-kappaB. Here we show that MyD88, a previously described protein of unknown function, is recruited to the IL-1 receptor complex following IL-1 stimulation. MyD88 binds to both IRAK (IL-1 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-kappaB. The C-terminus of MyD88 interacts with the IL-1 receptor and blocks NF-kappaB activation induced by IL-1, but not by TNF. Thus, MyD88 plays the same role in IL-1 signaling as TRADD and Tube do in TNF and Toll pathways, respectively: it couples a serine/threonine protein kinase to the receptor complex.

摘要

白细胞介素-1（IL-1）是一种促炎细胞因子，它通过由两条不同跨膜链组成的受体复合物发出信号，以产生多种细胞反应，包括激活转录因子核因子κB（NF-κB）。我们在此表明，髓样分化因子88（MyD88），一种先前描述的功能未知的蛋白质，在IL-1刺激后被招募到IL-1受体复合物。MyD88与白细胞介素-1受体相关激酶（IRAK）以及两条受体链的异源复合物（信号复合物）结合，从而介导IRAK与受体的结合。MyD88或其含死亡结构域的N端的异位表达激活NF-κB。MyD88的C端与IL-1受体相互作用，并阻断由IL-1而非肿瘤坏死因子（TNF）诱导的NF-κB激活。因此，MyD88在IL-1信号传导中发挥的作用与肿瘤坏死因子受体相关死亡结构域蛋白（TRADD）在TNF信号通路以及Tube在Toll信号通路中所起的作用相同：它将一种丝氨酸/苏氨酸蛋白激酶与受体复合物偶联起来。