5‐lipoxygenase‐activating protein is an arachidonate binding protein

JA Mancini, M Abramovitz, ME Cox, E Wong… - FEBS …, 1993 - Wiley Online Library
JA Mancini, M Abramovitz, ME Cox, E Wong, S Charleson, H Perrier, Z Wang, P Prasit…
FEBS letters, 1993Wiley Online Library
5‐Lipoxygenase‐activating protein (FLAP) is an 18‐kDa integral membrane protein which is
essential for cellular leukotriene (LT) synthesis, and is the target of LT biosynthesis
inhibitors. However, the mechanism by which FLAP activates 5‐LO has not been
determined. We have expressed high levels of human FLAP in Spodoptera frugiperda (Sf9)
insect cells infected with recombinant baculovirus, and used this system to demonstrate that
FLAP specifically binds [125I] L‐739,059, a novel photoaffinity analog of arachidonic acid …
5‐Lipoxygenase‐activating protein (FLAP) is an 18‐kDa integral membrane protein which is essential for cellular leukotriene (LT) synthesis, and is the target of LT biosynthesis inhibitors. However, the mechanism by which FLAP activates 5‐LO has not been determined. We have expressed high levels of human FLAP in Spodoptera frugiperda (Sf9) insect cells infected with recombinant baculovirus, and used this system to demonstrate that FLAP specifically binds [125I]L‐739,059, a novel photoaffinity analog of arachidonic acid. This binding is inhibited by both arachidonic acid and MK‐886, an LT biosynthesis inhibitor which specifically interacts with FLAP. These studies suggest that FLAP may activate 5‐LO by specifically binding arachidonic acid and transferring this substrate to the enzyme.
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