Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis

• Published in: Nature (London) Vol. 343; no. 6255; pp. 282 - 284
• Main Authors: Dixon, R. A. F, Diehl, R. E, Opas, E, Rands, E, Vickers, P. J, Evans, J. F, Gillard, J. W, Miller, D. K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 18.01.1990; Nature Publishing Group
• Subjects: 5-Lipoxygenase-Activating Proteins; Amino Acid Sequence; Analytical, structural and metabolic biochemistry; Animals; Arachidonate 5-lipoxygenase; Arachidonate 5-Lipoxygenase - metabolism; Arachidonate Lipoxygenases - metabolism; Arachidonic acid; Arthritis; Asthma; Base Sequence; Biochemistry; Biological activity; Biological and medical sciences; Bone cancer; Carrier Proteins; Cell Line; Cellular biology; Complementary DNA; Enzymes; Fatty acids; Fundamental and applied biological sciences. Psychology; Gene Expression; genes; Humans; Inflammation; Laboratories; Leukocytes; Leukotrienes; Leukotrienes - biosynthesis; Lipids; Lipoxygenase; man; Medical research; Membrane proteins; Membrane Proteins - genetics; Membrane Proteins - metabolism; Metabolites; Molecular Sequence Data; Molecules; Neutrophils; Osteosarcoma; Other biological molecules; Protein biosynthesis; Proteins; Psoriasis; Rats; Sequence Homology, Nucleic Acid; Skin diseases; Synthesis; Transfection; New York; United States > US; Human; Rat; Nucleotide sequence; Enzyme; Arachidonic acid derivatives; Rodentia; Biosynthesis; Inflammation; Gene expression; Leukotriene; Binding protein; Vertebrata; Mammalia; Cell line; Complementary DNA; Lipoxygenase; Aminoacid sequence
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/343282a0

Leukotrienes, the biologically active metabolites of arachidonic acid, have been implicated in a variety of inflammatory responses, including asthma, arthritis and psoriasis. Recently a compound, MK-886, has been described that blocks the synthesis of leukotrienes in intact activated leukocytes, but has little or no effect on enzymes involved in leukotriene synthesis, including 5-lipoxygenase, in cell-free systems. A membrane protein with a high affinity for MK-886 and possibly representing the cellular target for MK-886 has been isolated from rat and human leukocytes. Here, we report the isolation of a complementary DNA clone encoding the MK-886-binding protein. We also demonstrate that the expression of both the MK-886-binding protein and 5-lipoxygenase is necessary for leukotriene synthesis in intact cells. Because the MK-886-binding protein seems to play a part in activating this enzyme in cells, it is termed the five-lipoxygenase activating protein (FLAP).