Distinct parts of leukotriene C(4) synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein.
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Strid T, Svartz J, Franck N, Hallin E, Ingelsson B, Soderstrom M, Hammarstrom S
Distinct parts of leukotriene C(4) synthase interact with 5-lipoxygenase and 5-lipoxygenase activating protein.
Biochem Biophys Res Commun. 2009 Apr 17;381(4):518-22. doi: 10.1016/j.bbrc.2009.02.074. Epub 2009 Feb 20.
- PubMed ID
- 19233132 [ View in PubMed]
- 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.