Glutamyl-prolyl-tRNA synthetase 1 coordinates early endosomal anti-inflammatory AKT signaling

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Glutamyl-prolyl-tRNA synthetase 1 coordinates early endosomal anti-inflammatory AKT signaling
Eun-Young Lee; Su-Man Kim; Jung Hwan HwangSong Yee Jang; Shinhye Park; Sanghyeon Choi; Ga Seul Lee; Jungwon HwangJeong Hee Moon; P L Fox; S Kim; Chul-Ho LeeMyung Hee Kim
Bibliographic Citation
Nature Communications, vol. 13, pp. 6455-6455
Publication Year
The AKT signaling pathway plays critical roles in the resolution of inflammation. However, the underlying mechanisms of anti-inflammatory regulation and signal coordination remain unclear. Here, we report that anti-inflammatory AKT signaling is coordinated by glutamyl-prolyl-tRNA synthetase 1 (EPRS1). Upon inflammatory activation, AKT specifically phosphorylates Ser999 of EPRS1 in the cytoplasmic multi-tRNA synthetase complex, inducing release of EPRS1. EPRS1 compartmentalizes AKT to early endosomes via selective binding to the endosomal membrane lipid phosphatidylinositol 3-phosphate and assembles an AKT signaling complex specific for anti-inflammatory activity. These events promote AKT activation-mediated GSK3β phosphorylation, which increase anti-inflammatory cytokine production. EPRS1-deficient macrophages do not assemble the early endosomal complex and consequently exacerbate inflammation, decreasing the survival of EPRS1-deficient mice undergoing septic shock and ulcerative colitis. Collectively, our findings show that the housekeeping protein EPRS1 acts as a mediator of inflammatory homeostasis by coordinating compartment-specific AKT signaling.
Springer-Nature Pub Group
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Division of Biomedical Research > Microbiome Convergence Research Center > 1. Journal Articles
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
Division of Bio Technology Innovation > Core Research Facility & Analysis Center > 1. Journal Articles
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