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The Kinase Activity of Interleukin-1 Receptor–Associated Kinase 2 Is Essential for Lipopolysaccharide-Mediated Cytokine and Chemokine mRNA Stability and Translation

By Weiguo Yin, Youzhong Wan, Tae Whan Kim, Peng Yao, Hui Xiao, Hao Zhou, Jianhua Xiao, Paul Fox and Xiaoxia Li

Abstract

Interleukin-1 receptor–associated kinase 2 (IRAK2) has been shown to be essential for lipopolysaccharide (LPS)-mediated posttranscriptional control of cytokine and chemokine production. In this study, we investigated the role of IRAK2 kinase activity in LPS-mediated posttranscriptional control by reconstituting IRAK2-deficient macrophages with either wild-type or kinase-inactive IRAK2. Compared with wild-type IRAK2 (IRAK2-WT) macrophages, kinase-inactive IRAK2 (IRAK2-KD) macrophages show reduced cytokine and chemokine mRNA stability and translation in response to LPS. Further, LPS-treated IRAK2-KD macrophages also show reduced activation of MKK3/6, MNK1, and eIF4E and attenuated toll-like receptor 4-induced tristetraprolin modification and stabilization. Taken together, these results suggest that the kinase activity of IRAK2 is required for the optimal activation of mitogen-activated protein kinase signaling, which regulates cytokine and chemokine production at posttranscriptional levels

Topics: Research Reports
Publisher: Mary Ann Liebert, Inc.
OAI identifier: oai:pubmedcentral.nih.gov:3083721
Provided by: PubMed Central
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