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

RAF Dixon, RE Diehl, E Opas, E Rands, PJ Vickers… - Nature, 1990 - nature.com
RAF Dixon, RE Diehl, E Opas, E Rands, PJ Vickers, JF Evans, JW Gillard, DK Miller
Nature, 1990nature.com
LEUKOTRIENES, the biologically active metabolites of arachidonic acid, have been
implicated in a variety of inflammatory responses, including asthma, arthritis and psoriasis1,
2. 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 systems3. A membrane protein
with a high affinity for MK-886 and possibly representing the cellular target for MK-886 has …
Abstract
LEUKOTRIENES, the biologically active metabolites of arachidonic acid, have been implicated in a variety of inflammatory responses, including asthma, arthritis and psoriasis1,2. 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 systems3. 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 leukocytes4. 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).
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