TY  - JOUR
A1  - Basavarajappa, Devaraj
A1  - Wan, Min
A1  - Lukic, Ana
A1  - Steinhilber, Dieter
A1  - Samuelsson, Bengt
A1  - Rådmark, Olof
T1  - Roles of coactosin-like protein (CLP) and 5-lipoxygenase-activating protein (FLAP) in cellular leukotriene biosynthesis
T2  - Proceedings of the National Academy of Sciences of the United States of America
N2  - 5-Lipoxygenase (5LO) is a key enzyme in biosynthesis of leukotrienes (LTs), lipid mediators of inflammation. To study the roles of the 5LO accessory proteins coactosin-like protein (CLP) and 5LO-activating protein (FLAP), we knocked down these proteins in human monocytic cells. Our results show that expression of CLP was required for full cellular 5LO activity when cells were activated with Ca2+ ionophore, as well as with a physiological stimulus (lipopolysaccharide followed by N-formylmethionyl-leucyl-phenylalanine). During LT biosynthesis in stimulated cells, 5LO typically translocates to the nuclear membrane. This redistribution, from cytosolic to perinuclear, was clearly compromised in both CLP- and FLAP-deficient cells. Our results suggest that the CLP–5LO interaction may be a target for reduced LT production.
KW  - inflammation
KW  - eicosanoid
KW  - oxylipin
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/35263
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-352636
SN  - 0027-8424
SN  - 1091-6490
N1  - Freely available online through the PNAS open access option.
VL  - 111
IS  - 31
SP  - 11371
EP  - 11376
PB  - National Acad. of Sciences
CY  - Washington, DC
ER  -