5-LIPOXYGENASE-ACTIVATING PROTEIN IS AN ARACHIDONATE BINDING-PROTEIN

被引：182

作者：

MANCINI, JA

ABRAMOVITZ, M

COX, ME

WONG, E

CHARLESON, S

PERRIER, H

WANG, ZY

PRASIT, P

VICKERS, PJ

机构：

[1] MERCK FROSST CTR THERAPEUT RES,DEPT PHARMACOL,POB 1005,POINTE CLAIRE H9R 4P8,PQ,CANADA

[2] MERCK FROSST CTR THERAPEUT RES,DEPT MOLEC BIOL,POINTE CLAIRE H9R 4P8,PQ,CANADA

[3] MERCK FROSST CTR THERAPEUT RES,DEPT MED CHEM,POINTE CLAIRE H9R 4P8,PQ,CANADA

来源：

FEBS LETTERS | 1993年 / 318卷 / 03期

关键词：

5-LIPOXYGENASE-ACTIVATING PROTEIN; 5-LIPOXYGENASE; ARACHIDONIC ACID; PHOTOAFFINITY LABELING; BACULOVIRUS;

D O I：

10.1016/0014-5793(93)80528-3

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 [I-125]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.

引用

页码：277 / 281

页数：5

共 27 条

[1] PHARMACOLOGY OF MK-0591 (3-[1-(4-CHLOROBENZYL)-3-(T-BUTYLTHIO)-5-(QUINOLIN-2-YL-METHOXY)-INDOL-2-YL]-2,2-DIMETHYL PROPANOIC ACID), A POTENT, ORALLY ACTIVE LEUKOTRIENE BIOSYNTHESIS INHIBITOR [J].

BRIDEAU, C ;

CHAN, C ;

CHARLESON, S ;

DENIS, D ;

EVANS, JF ;

FORDHUTCHINSON, AW ;

FORTIN, R ;

GILLARD, JW ;

GUAY, J ;

GUEVREMONT, D ;

HUTCHINSON, JH ;

JONES, TR ;

LEGER, S ;

MANCINI, JA ;

MCFARLANE, CS ;

PICKETT, C ;

PIECHUTA, H ;

PRASIT, P ;

RIENDEAU, D ;

ROUZER, CA ;

TAGARI, P ;

VICKERS, PJ ;

YOUNG, RN ;

ABRAHAM, WM .

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 1992, 70 (06) :799-807

[2]

CHARLESON S, 1992, MOL PHARMACOL, V41, P873

[3] REQUIREMENT OF A 5-LIPOXYGENASE-ACTIVATING PROTEIN FOR LEUKOTRIENE SYNTHESIS [J].

DIXON, RAF ;

DIEHL, RE ;

OPAS, E ;

RANDS, E ;

VICKERS, PJ ;

EVANS, JF ;

GILLARD, JW ;

MILLER, DK .

NATURE, 1990, 343 (6255) :282-284

[4]

FORDHUTCHINSON AW, 1989, LEUKOTRIENES LIPOXYG, V2, P405

[5] L-663,536 (MK-886) (3-[1-(4-CHLOROBENZYL)-3-T-BUTYL-THIO-5-ISOPROPYLINDOL-2-YL]-2,2-DIMETHYLPROPANOIC ACID), A NOVEL, ORALLY ACTIVE LEUKOTRIENE BIOSYNTHESIS INHIBITOR [J].

GILLARD, J ;

FORDHUTCHINSON, AW ;

CHAN, C ;

CHARLESON, S ;

DENIS, D ;

FOSTER, A ;

FORTIN, R ;

LEGER, S ;

MCFARLANE, CS ;

MORTON, H ;

PIECHUTA, H ;

RIENDEAU, D ;

ROUZER, CA ;

ROKACH, J ;

YOUNG, R ;

MACINTYRE, DE ;

PETERSON, L ;

BACH, T ;

EIERMANN, G ;

HOPPLE, S ;

HUMES, J ;

HUPE, L ;

LUELL, S ;

METZGER, J ;

MEURER, R ;

MILLER, DK ;

OPAS, E ;

PACHOLOK, S .

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 1989, 67 (05) :456-464

[6]

Hanahan D., 1985, DNA CLONING PRACTICA, P109

[7]

JONES TR, 1989, LEUKOTRIENES LIPOXYG, V2, P309

[8]

KARGMAN S, 1991, J BIOL CHEM, V266, P23745

[9] THE BIOLOGICALLY-ACTIVE LEUKOTRIENES - BIOSYNTHESIS, METABOLISM, RECEPTORS, FUNCTIONS, AND PHARMACOLOGY [J].

LEWIS, RA ;

AUSTEN, KF .

JOURNAL OF CLINICAL INVESTIGATION, 1984, 73 (04) :889-897

[10]

LEWIS RA, 1990, NEW ENGL J MED, V323, P645

← 1 2 3 →