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Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response

Cited 110 time in Web of Science Cited 117 time in Scopus
Authors
Park, Sang Gyu; Kim, Hye Jin; Min, You Hong; Choi, Eung-Chil; Shin, Young Kee; Park, Bum-Joon; Lee, Sang Won; Kim, Sunghoon
Issue Date
2005
Publisher
National Academy of Sciences
Citation
PNAS; Vol.102(18); pp.6356-6361
Keywords
aminoacyl-tRNA synthetasecytokineTNF-αimmune responsecell migration
Abstract
Although aminoacyl-tRNA synthetases (ARSs) are essential for protein synthesis, they also function as regulators and signaling molecules in diverse biological processes. Here, we screened 11 different human ARSs to identify the enzyme that is secreted as a signaling molecule. Among them, we found that lysyl-tRNA synthetase (KRS) was secreted from intact human cells, and its secretion was induced by TNF-α. The secreted KRS bound to macrophages and peripheral blood mononuclear cells to enhance the TNF-α production and their migration. The mitogen-activated protein kinases, extracellular signal-regulated kinase and p38 mitogen-activated protein kinase, and Gαi were determined to be involved in the signal transduction triggered by KRS. All of these activities demonstrate that human KRS may work as a previously uncharacterized signaling molecule, inducing immune response through the activation of monocyte/macrophages.
ISSN
0027-8424
Language
English
URI
http://hdl.handle.net/10371/73411
DOI
https://doi.org/10.1073/pnas.0500226102
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College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
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