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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


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.
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Provided by: PubMed Central
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