期刊论文详细信息
PLoS Pathogens
Pathogen Recognition Receptor Signaling Accelerates Phosphorylation-Dependent Degradation of IFNAR1
Darren P. Baker1  Juan Qian2  Serge Y. Fuchs2  Jianghuai Liu2  N. Adrian Leu2  Wei-Chun HuangFu2  Hui Zheng2  Christopher J. Carbone2 
[1] BiogenIdec, Cambridge, Massachusetts, United States of America;Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
关键词: Phosphorylation;    Immune receptor signaling;    Immunoprecipitation;    Cytokines;    Vesicular stomatitis virus;    Interferons;    In vitro kinase assay;    Kinase inhibitors;   
DOI  :  10.1371/journal.ppat.1002065
学科分类:生物科学(综合)
来源: Public Library of Science
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【 摘 要 】

An ability to sense pathogens by a number of specialized cell types including the dendritic cells plays a central role in host's defenses. Activation of these cells through the stimulation of the pathogen-recognition receptors induces the production of a number of cytokines including Type I interferons (IFNs) that mediate the diverse mechanisms of innate immunity. Type I IFNs interact with the Type I IFN receptor, composed of IFNAR1 and IFNAR2 chains, to mount the host defense responses. However, at the same time, Type I IFNs elicit potent anti-proliferative and pro-apoptotic effects that could be detrimental for IFN-producing cells. Here, we report that the activation of p38 kinase in response to pathogen-recognition receptors stimulation results in a series of phosphorylation events within the IFNAR1 chain of the Type I IFN receptor. This phosphorylation promotes IFNAR1 ubiquitination and accelerates the proteolytic turnover of this receptor leading to an attenuation of Type I IFN signaling and the protection of activated dendritic cells from the cytotoxic effects of autocrine or paracrine Type I IFN. In this paper we discuss a potential role of this mechanism in regulating the processes of innate immunity.

【 授权许可】

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