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Distinct parts of leukotriene C(4) synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2009 Apr 17; Vol. 381 (4), pp. 518-22. Date of Electronic Publication: 2009 Feb 20. - Publication Year :
- 2009
-
Abstract
- Leukotriene C(4) is a potent inflammatory mediator formed from arachidonic acid and glutathione. 5-Lipoxygenase (5-LO), 5-lipoxygenase activating protein (FLAP) and leukotriene C(4) synthase (LTC(4)S) participate in its biosynthesis. We report evidence that LTC(4)S interacts in vitro with both FLAP and 5-LO and that these interactions involve distinct parts of LTC(4)S. FLAP bound to the N-terminal part/first hydrophobic region of LTC(4)S. This part did not bind 5-LO which bound to the second hydrophilic loop of LTC(4)S. Fluorescent FLAP- and LTC(4)S-fusion proteins co-localized at the nuclear envelope. Furthermore, GFP-FLAP and GFP-LTC(4)S co-localized with a fluorescent ER marker. In resting HEK293/T or COS-7 cells GFP-5-LO was found mainly in the nuclear matrix. Upon stimulation with calcium ionophore, GFP-5-LO translocated to the nuclear envelope allowing it to interact with FLAP and LTC(4)S. Direct interaction of 5-LO and LTC(4)S in ionophore-stimulated (but not un-stimulated) cells was demonstrated by BRET using GFP-5-LO and Rluc-LTC(4)S.
- Subjects :
- 5-Lipoxygenase-Activating Proteins
Animals
COS Cells
Carrier Proteins antagonists & inhibitors
Chlorocebus aethiops
Fluorescence Resonance Energy Transfer methods
Glutathione Transferase genetics
Humans
Membrane Proteins antagonists & inhibitors
Arachidonate 5-Lipoxygenase metabolism
Carrier Proteins metabolism
Glutathione Transferase metabolism
Membrane Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2104
- Volume :
- 381
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 19233132
- Full Text :
- https://doi.org/10.1016/j.bbrc.2009.02.074