ArticleProceedings of the National Academy of Sciences of the United States of America1994
Expression cloning of a cDNA for human leukotriene C4 synthase, an integral membrane protein conjugating reduced glutathione to leukotriene A4.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 297 citations in OpenAlex.
- Potential mechanisms and effects of AFB1-induced asthma: A comprehensive analysis based on network toxicology and molecular docking.PloS one · 2026Article
- Intestinal mast cell-derived leukotrienes mediate the anaphylactic response to ingested antigens.Science (New York, N.Y.) · 2025Article
- Leukotrienes: Bridging the Inflammatory Gap in Asthma and Inflammatory Bowel Diseases (IBD).Comprehensive Physiology · 2025Review
- Roles of Lipoxygenases in Cardiovascular Diseases.Journal of cardiovascular translational research · 2025Review
- Targeting leukotriene biosynthesis to prevent atherosclerotic cardiovascular disease.Conditioning medicine · 2023Article
- Short-term high fat feeding induces inflammatory responses of tuft cells and mucosal barrier cells in the murine stomach.Histology and histopathology · 2023Article
- Review
- Leukotriene DThe Journal of allergy and clinical immunology · 2021Article
- Metabolism pathways of arachidonic acids: mechanisms and potential therapeutic targets.Signal transduction and targeted therapy · 2021Review
- Aspirin Actions in Treatment of NSAID-Exacerbated Respiratory Disease.Frontiers in immunology · 2021Review
- Platelet-Adherent Leukocytes Associated With Cutaneous Cross-Reactive Hypersensitivity to Nonsteroidal Anti-Inflammatory Drugs.Frontiers in pharmacology · 2020Article
- Function of secreted phospholipase ABiochimica et biophysica acta. Molecular and cell biology of lipids · 2019Review
- COX-1 mediates IL-33-induced extracellular signal-regulated kinase activation in mast cells: Implications for aspirin sensitivity.The Journal of allergy and clinical immunology · 2019Article
- BLT1 in dendritic cells promotes Th1/Th17 differentiation and its deficiency ameliorates TNBS-induced colitis.Cellular & molecular immunology · 2018Article
- Leukotriene biosynthetic enzymes as therapeutic targets.The Journal of clinical investigation · 2018Review
- Type 2 Cysteinyl Leukotriene Receptors Drive IL-33-Dependent Type 2 Immunopathology and Aspirin Sensitivity.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Pharmacological profile and efficiency in vivo of diflapolin, the first dual inhibitor of 5-lipoxygenase-activating protein and soluble epoxide hydrolase.Scientific reports · 2017Article
- Role of the Cysteinyl Leukotrienes in the Pathogenesis and Progression of Cardiovascular Diseases.Mediators of inflammation · 2017Review
- Phosphorylation of Leukotriene C4 Synthase at Serine 36 Impairs Catalytic Activity.The Journal of biological chemistry · 2016Article
- Phosphoinositide 3-Kinase δ Regulates Dectin-2 Signaling and the Generation of Th2 and Th17 Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Leukotriene (LT) C4 synthase, an integral microsomal membrane protein, conjugates LTA4, an epoxide intermediate, to reduced glutathione (GSH) to form a proinflammatory mediator, LTC4. A sensitive fluorescence-linked immunoassay for LTC4 was used to screen a KG-1 cDNA expression library for LTC4 synthase activity after transfection of COS cells and addition of substrate LTA4. Stepwise resolution of 240,000 colonies in 96 pools led to the identification of individual clones with maximal LTC4 synthase activity that contained a 694-bp cDNA insert. This insert was composed of a 54-bp 5' nontranslated region, an ATTAAA polyadenylylation signal, and a poly(A)+ tail. The open reading frame encodes a 16.5-kDa protein with a pI of 11.05. Hybridization with a cDNA probe demonstrated a mRNA transcript of 0.7 kbp in RNAs from human eosinophils and KG-1 cells, which contain LTC4 synthase. The nucleotide and deduced amino acid sequences of the LTC4 synthase cDNA show no significant homology to GSH S-transferases but share 31% overall amino acid identity with 5-lipoxygenase activating protein (FLAP). The identity at the N-terminal two-thirds of these two proteins is 44%, with some regions of near identity. Peptide structural analysis of the deduced LTC4 synthase predicts the presence of three transmembrane domains nearly superimposable on those of FLAP. Moreover, LTC4 synthase is inhibitable by a FLAP inhibitor, MK-886. Therefore, LTC4 synthase is distinct from the known GSH S-transferases by nucleotide and consensus amino acid sequences, and its GSH-conjugating function represents a distinct integral membrane protein belonging to a distinct gene family.
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