期刊
EMBO JOURNAL
卷 23, 期 1, 页码 100-110出版社
WILEY
DOI: 10.1038/sj.emboj.7600033
关键词
death domain; IRAK; MyD88; Pelle; Toll; Tube
资金
- NCATS NIH HHS [KL2 TR000118] Funding Source: Medline
- NIGMS NIH HHS [5R01-GM50545, R01 GM050545] Funding Source: Medline
In Drosophila, the Toll pathway establishes the embryonic dorsoventral axis and triggers innate immune responses to infection. The transmembrane receptor Toll acts through three death domain-containing proteins, the kinase Pelle and the adapters Tube and MyD88, in signaling to downstream NF-kappaB-like transcription factors. Here, we delineate the critical events in the earliest stages of Toll signaling. Mutational studies based on structural modeling reveal that the direct interaction of the bivalent Tube death domain with MyD88 is critical for signaling in vivo. The complex of MyD88 and Tube forms prior to signaling and is localized to the embryonic plasma membrane by MyD88. Upon Toll homodimerization, this complex is rapidly recruited to Toll. Binding of Pelle to the MyD88 Tube complex promotes Pelle activation, leading to degradation of the IkappaB-like inhibitor, Cactus. Together, these experiments convert a linear picture of gene function into a dynamic mechanistic and structural understanding of signaling complex assembly and function.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据