TRNA Synthetase as a Cytokine

Abstract

Aminoacyl-tRNA synthetases (ARSs) have diverse biological functions beyond that of protein synthesis. Park et al. cloned the 17 human ARSs into human embryonic kidney 293 (HEK293) cells and screened the conditioned medium from the 11 ARS clones that were highly expressed. Lysyl-tRNA synthetase (KRS) was detectable in the medium, and analysis of various cell lines showed that tumor necrosis factor α (TNF-α) stimulated KRS secretion of between 0.4 and 1% of total cellular KRS in a subset of these cells, including HCT116 colon cancer cells. When added to immune cell lines, KRS exhibited saturable binding to the cell surface. Addition of KRS, but not tryptophanyl tRNA synthetase (WRS), to the RAW264.7 macrophage cell line inhibited cell proliferation, stimulated TNF-α secretion, stimulated metalloproteinase 9 activity, and stimulated chemokinesis. Pharmacological inhibitors were used to show that Gα i and the mitogen-activated protein kinase (MAPK) cascades involving p38 and ERK were involved in mediating the effects of KRS on the RAW264.7 cells. Thus, KRS joins the list of ARSs that have noncanonical signaling functions. S. G. Park, H. J. Kim, Y. H. Min, E.-C. Choi, Y. K. Shin, B.-J. Park, S. W. Lee, S. Kim, Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response. Proc. Nat. Acad. Sci. U.S.A. 102 , 6356-6361 (2005). [Abstract] [Full Text]