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Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response
Sang Gyu Park *,
Hye Jin Kim *,
You Hong Min,
Young Kee Shin,
Sang Won Lee, and
National Creative Research Initiatives Center for ARS Network, College of Pharmacy, Seoul National University, Seoul 151-742, Korea
Edited by Paul R. Schimmel, The Scripps Research Institute, La Jolla, CA, and approved March 22, 2005
Received for publication January 11, 2005.
Although aminoacyl-tRNA synthetases (ARSs) are essential forprotein synthesis, they also function as regulators and signalingmolecules in diverse biological processes. Here, we screened11 different human ARSs to identify the enzyme that is secretedas a signaling molecule. Among them, we found that lysyl-tRNAsynthetase (KRS) was secreted from intact human cells, and itssecretion was induced by TNF-. The secreted KRS bound to macrophagesand peripheral blood mononuclear cells to enhance the TNF- productionand their migration. The mitogen-activated protein kinases,extracellular signal-regulated kinase and p38 mitogen-activatedprotein kinase, and Gi were determined to be involved in thesignal transduction triggered by KRS. All of these activitiesdemonstrate that human KRS may work as a previously uncharacterizedsignaling molecule, inducing immune response through the activationof monocyte/macrophages.