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Publication : Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response.

First Author  Park SG Year  2005
Journal  Proc Natl Acad Sci U S A Volume  102
Issue  18 Pages  6356-61
PubMed ID  15851690 Mgi Jnum  J:240288
Mgi Id  MGI:5882898 Doi  10.1073/pnas.0500226102
Citation  Park SG, et al. (2005) Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response. Proc Natl Acad Sci U S A 102(18):6356-61
abstractText  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-alpha. The secreted KRS bound to macrophages and peripheral blood mononuclear cells to enhance the TNF-alpha production and their migration. The mitogen-activated protein kinases, extracellular signal-regulated kinase and p38 mitogen-activated protein kinase, and Galphai 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.
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