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Proc Natl Acad Sci U S A. 2005 May 3;102(18):6356-61. Epub 2005 Apr 25.

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

Author information

  • 1National Creative Research Initiatives Center for ARS Network, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.

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 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.

PMID:
15851690
[PubMed - indexed for MEDLINE]
PMCID:
PMC1088368
Free PMC Article

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