Proceedings of the National Academy of Sciences · 2005 · 180 citations · 49 references
Life SciencesImmunologyMolecular BiologyCell SignalingInnate ImmunitySignal TransductionImmune SignalingInflammatory SignalingInnate Immune Signaling PathwaysMacrophage BiologyProtein SynthesisSignal Transduction PathwaysAminoacyl-transfer Rna SynthetasesAminoacyl-trna SynthetasesExtracellular Signal-regulated Kinase PathwayExtracellular Signal-regulated Kinase SignalingInflammatory Signal TransductionMitogen-activated Protein Kinase CascadesMitogen-activated Protein Kinase PathwaysP38 Mitogen-activated Protein Kinase Signaling
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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Mutation of the mouse klotho gene leads to a syndrome resembling ageing.
PubMed · 1997 · 66.6K citations
ASK1 is required for sustained activations of JNK/p38 MAP kinases and apoptosis
Kei Tobiume, Atsushi Matsuzawa, Takumi Takahashi et al. · EMBO Reports · 2001 · 1.2K citations · Full text