Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis.
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Dixon RA, Diehl RE, Opas E, Rands E, Vickers PJ, Evans JF, Gillard JW, Miller DK
Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis.
Nature. 1990 Jan 18;343(6255):282-4.
- PubMed ID
- 2300173 [ View in PubMed]
- Abstract
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).