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

Authors:
  • RDR. E. Diehl
    R. E. Diehl
  • EOE. Opas
    E. Opas
  • ERE. Rands
    E. Rands
  • PVP. J. Vickers
    P. J. Vickers
  • JEJ. F. Evans
    J. F. Evans
  • JGJ. W. Gillard
    J. W. Gillard
  • DMD. K. Miller
    D. K. Miller
Publisher website
Google Scholar
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).

This publication has 18 references indexed in Scilit: