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Identification and isolation of a membrane protein necessary for leukotriene production

Nature volume 343, pages 278–281 (1990)Cite this article

Abstract

SEVERAL inflammatory diseases, including asthma, arthritis and psoriasis are associated with the production of leukotrienes by neutrophils, mast cells and macrophages1–3. The initial enzymatic step in the formation of leukotrienes is the oxidation of arachidonic acid by 5-lipoxygenase (5-LO) to leukotriene A4 (refs 4–6). Osteosarcoma cells transfected with 5-LO express active enzyme in broken cell preparations, but no leukotriene metabolites are produced by these cells when stimulated with the calcium ionophore A23187, indicating that an additional component is necessary for cellular 5-LO activity7. A new class of indole leukotriene inhibitor has been described that inhibits the formation of cellular leukotrienes but has no direct inhibitory effect on soluble 5-LO activity8. We have now used these potent agents to identify and isolate a novel membrane protein of relative molecular mass 18,000 which is necessary for cellular leukotriene synthesis.

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Author information

Author notes

  1. Claire Léveillé

    Present address: Immunology Laboratory, École de Médecine Dentaire, Université Laval, Québec, 61K7P4, Canada

  2. Carol Rouzer

    Present address: Department of Chemistry, Western Maryland College, Westminster, Maryland, 21157, USA

  3. Irving S. Sigal: Deceased.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Merck Institute for Therapeutic Research, PO Box 2000, Rahway, New Jersey, 07065, USA

    Douglas K. Miller, Sharon Sadowski, Ronda Rosen, Irving S. Sigal & Catherine D. Strader

  2. Department of Medicinal Chemistry, Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Québec, H9R 4P8, Canada

    John W. Gillard, Peter Charleson, Réjean Fortin & Jacques Yves Gauthier

  3. Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Québec, H9R 4P8, Canada

    Philip J. Vickers, Claire Léveillé, Joseph A. Mancini, Anthony W. Ford-Hutchinson, Carol Rouzer & Jilly F. Evans

  4. Department of Molecular Biology, Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania, 19486, USA

    Richard A. F. Dixon, John Rodkey & Irving S. Sigal

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  1. Douglas K. Miller
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  11. Jacques Yves Gauthier
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  14. Carol Rouzer
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  15. Irving S. Sigal
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  17. Jilly F. Evans
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Miller, D., Gillard, J., Vickers, P. et al. Identification and isolation of a membrane protein necessary for leukotriene production. Nature 343, 278–281 (1990). https://doi.org/10.1038/343278a0

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