Human lysyl-tRNA synthetase is secreted to trigger proinflammatory response.
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.
Park
Sang Gyu
SG
National Creative Research Initiatives Center for ARS Network, College of Pharmacy, Seoul National University, Seoul 151-742, Korea.
Kim
Hye Jin
HJ
Min
You Hong
YH
Choi
Eung-Chil
EC
Shin
Young Kee
YK
Park
Bum-Joon
BJ
Lee
Sang Won
SW
Kim
Sunghoon
S
D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D006801:Humans; D008250:Lysine-tRNA Ligase / Q000378:metabolism*; D008262:Macrophage Activation / Q000276:immunology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism* / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; C000613080:KARS1 protein, human; D008250:Lysine-tRNA Ligase