title: The kinase activity of interleukin-1 receptor-associated kinase 2 is essential for lipopolysaccharide-mediated cytokine and chemokine mRNA stability and translation.
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.
authors.affiliation: Department of Microbiology and Immunology, University of South China, Hengyang Hunan, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Yin
authors.forename: Youzhong
authors.initials: Y
authors.lastname: Wan
authors.forename: Tae Whan
authors.initials: TW
authors.lastname: Kim
authors.forename: Peng
authors.initials: P
authors.lastname: Yao
authors.forename: Hui
authors.initials: H
authors.lastname: Xiao
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.forename: Jianhua
authors.initials: J
authors.lastname: Xiao
authors.forename: Paul
authors.initials: P
authors.lastname: Fox
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics*; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D053592:Interleukin-1 Receptor-Associated Kinases / Q000276:immunology* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000378:metabolism / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D020871:RNA Stability; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D053592:Interleukin-1 Receptor-Associated Kinases; D020929:Mitogen-Activated Protein Kinase Kinases