ArticleThe Journal of biological chemistry2018
Tryptophanyl-tRNA synthetase mediates high-affinity tryptophan uptake into human cells.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Human aminoacyl-tRNA synthetases as integrators of translation and cell signalling networks.Nature reviews. Molecular cell biology · 2026Review
- Aminoacyl-tRNA synthetases in tumor immunity: canonical translation, source-resolved immune circuits and therapeutic opportunities.Frontiers in immunology · 2026Review
- IDO and TDO inhibitors in cancer immunotherapy: mechanisms, clinical development, and future directions.Frontiers in pharmacology · 2025Review
- Review
- The high-affinity tryptophan uptake transport system in human cells.Biochemical Society transactions · 2024Review
- Discovery of the sEH Inhibitor Epoxykynin as a Potent Kynurenine Pathway Modulator.Journal of medicinal chemistry · 2024Article
- Article
- The effect of TLR3 priming conditions on MSC immunosuppressive properties.Stem cell research & therapy · 2023Article
- Tryptophan-Starved Human Cells Overexpressing Tryptophanyl-tRNA Synthetase Enhance High-Affinity Tryptophan Uptake via Enzymatic Production of Tryptophanyl-AMP.International journal of molecular sciences · 2023Article
- Identification of a Novel Pseudo-Natural Product Type IV IDO1 Inhibitor Chemotype.Angewandte Chemie (International ed. in English) · 2022Article
- A novel gene signature unveils three distinct immune-metabolic rewiring patterns conserved across diverse tumor types and associated with outcomes.Frontiers in immunology · 2022Article
- Tryptophanyl-tRNA Synthetase as a Potential Therapeutic Target.International journal of molecular sciences · 2021Review
- Tryptophanyl-tRNA Synthetase Sensitizes Hormone Receptor-Positive Breast Cancer to Docetaxel-Based Chemotherapy.Journal of breast cancer · 2020Article
- Article
- Article
- Design and synthesis of novel spirooxindole-indenoquinoxaline derivatives as novel tryptophanyl-tRNA synthetase inhibitors.Molecular diversity · 2020Article
- Prognostic Implications of Metabolism Related Gene Signature in Cutaneous Melanoma.Frontiers in oncology · 2020Article
- Roles of Aminoacyl-tRNA Synthetases in Cancer.Frontiers in cell and developmental biology · 2020Review
- Article
- Not your usual tRNA synthetase: hWARS serves as an enterovirus entry factor.The Journal of clinical investigation · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The tryptophan (Trp) transport system has a high affinity and selectivity toward Trp, and has been reported to exist in both human and mouse macrophages. Although this system is highly expressed in interferon-γ (IFN-γ)-treated cells and indoleamine 2,3-dioxygenase 1 (IDO1)-expressing cells, its identity remains incompletely understood. Tryptophanyl-tRNA synthetase (TrpRS) is also highly expressed in IFN-γ-treated cells and also has high affinity and selectivity for Trp. Here, we investigated the effects of human TrpRS expression on Trp uptake into IFN-γ-treated human THP-1 monocytes or HeLa cells. Inhibition of human TrpRS expression by TrpRS-specific siRNAs decreased and overexpression of TrpRS increased Trp uptake into the cells. Of note, the TrpRS-mediated uptake system had more than hundred-fold higher affinity for Trp than the known System L amino acid transporter, promoted uptake of low Trp concentrations, and had very high Trp selectivity. Moreover, site-directed mutagenesis experiments indicated that Trp- and ATP-binding sites, but not tRNA-binding sites, in TrpRS are essential for TrpRS-mediated Trp uptake into the human cells. We further demonstrate that the addition of purified TrpRS to cell culture medium increases Trp uptake into cells. Taken together, our results reveal that TrpRS plays an important role in high-affinity Trp uptake into human cells.
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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.