ArticleThe Journal of biological chemistry2019
Matrix metalloproteinases inactivate the proinflammatory functions of secreted moonlighting tryptophanyl-tRNA synthetase.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 22 citations in OpenAlex.
- Prognostic Value of Tryptophanyl-tRNA Synthetase in Sepsis Combined with Kidney Dysfunction or Urinary Tract Infection: A Prospective Observational Study.Diagnostics (Basel, Switzerland) · 2025Article
- Aminoacyl-tRNA synthetase interactions in SARS-CoV-2 infection.Biochemical Society transactions · 2023Review
- Plasma proteome of growing tumors.Scientific reports · 2023Article
- Mechanistic perspectives on anti-aminoacyl-tRNA synthetase syndrome.Trends in biochemical sciences · 2023Review
- ClearColi as a platform for untagged pneumococcal surface protein A production: cultivation strategy, bioreactor culture, and purification.Applied microbiology and biotechnology · 2022Article
- The pathophyiological role of aminoacyl-tRNA synthetases in digestive system diseases.Frontiers in physiology · 2022Review
- Tryptophanyl-tRNA Synthetase as a Potential Therapeutic Target.International journal of molecular sciences · 2021Review
- Towards Understanding COVID-19: Molecular Insights, Co-infections, Associated Disorders, and Aging.Journal of Alzheimer's disease reports · 2021Article
- Extracellular tyrosyl-tRNA synthetase cleaved by plasma proteinases and stored in platelet α-granules: Potential role in monocyte activation.Research and practice in thrombosis and haemostasis · 2020Article
- Moonlighting matrix metalloproteinase substrates: Enhancement of proinflammatory functions of extracellular tyrosyl-tRNA synthetase upon cleavage.The Journal of biological chemistry · 2020Article
- Pharmacological Targets of Kaempferol Within Inflammatory Pathways-A Hint Towards the Central Role of Tryptophan Metabolism.Antioxidants (Basel, Switzerland) · 2020Article
- Roles of aminoacyl-tRNA synthetases in immune regulation and immune diseases.Cell death & disease · 2019Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 3 countries.
Funding
Abstract
Tryptophanyl-tRNA synthetase (WRS) is a cytosolic aminoacyl-tRNA synthetase essential for protein synthesis. WRS is also one of a growing number of intracellular proteins that are attributed distinct noncanonical "moonlighting" functions in the extracellular milieu. Moonlighting aminoacyl-tRNA synthetases regulate processes such as inflammation, but how these multifunctional enzymes are themselves regulated remains unclear. Here, we demonstrate that WRS is secreted from human macrophages, fibroblasts, and endothelial cells in response to the proinflammatory cytokine interferon γ (IFNγ). WRS signaled primarily through Toll-like receptor 2 (TLR2) in macrophages, leading to phosphorylation of the p65 subunit of NF-κB with associated loss of NF-κB inhibitor α (IκB-α) protein. This signaling initiated secretion of tumor necrosis factor α (TNFα) and CXCL8 (IL8) from macrophages. We also demonstrated that WRS is a potent monocyte chemoattractant. Of note, WRS increased matrix metalloproteinase (MMP) activity in the conditioned medium of macrophages in a TNFα-dependent manner. Using purified recombinant proteins and LC-MS/MS to identify proteolytic cleavage sites, we demonstrated that multiple MMPs, but primarily macrophage MMP7 and neutrophil MMP8, cleave secreted WRS at several sites. Loss of the WHEP domain following cleavage at Met
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.