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PNAS 102 (18): 6356-6361

Copyright © 2005 by the National Academy of Sciences.

From The Cover

CELL BIOLOGY

Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response

Sang Gyu Park *, Hye Jin Kim *, You Hong Min, Eung-Chil Choi, Young Kee Shin, Bum-Joon Park, Sang Won Lee, and Sunghoon Kim {dagger}

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.

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-{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 G{alpha}i 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.

Key Words: aminoacyl-tRNA synthetase • cytokine • TNF-{alpha} • immune response • cell migration

This paper was submitted directly (Track II) to the PNAS office.

Abbreviations: ARS, aminoacyl-tRNA synthetase; ERK, extracellular signal-regulated kinase; G{alpha}i, inhibitory G protein; KRS, lysyl-tRNA synthetase; MAPK, mitogen-activated protein kinase; MMP, matrix metalloproteinase; PBMC, peripheral blood mononuclear cell; WRS, tryptophanyl-tRNA synthetase.

* S.G.P. and H.J.K. contributed equally to the work.

{dagger} To whom correspondence should be addressed. E-mail: sungkim{at}snu.ac.kr.

© 2005 by The National Academy of Sciences of the USA

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