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5‐lipoxygenase‐activating protein is an arachidonate binding protein
Author(s) -
Mancini Joseph A.,
Abramovitz Mark,
Cox Martha E.,
Wong Elizabeth,
Charleson Stella,
Perrier Hélène,
Wang Zhaoyin,
Prasit Peptiboon,
Vickers Philip J.
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)80528-3
Subject(s) - arachidonic acid , sf9 , lipoxygenase , biosynthesis , spodoptera , leukotriene , biochemistry , arachidonate 5 lipoxygenase , recombinant dna , chemistry , enzyme , photoaffinity labeling , binding protein , binding site , microbiology and biotechnology , biology , gene , immunology , asthma
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 [ 125 I]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.