Proceedings of the National Academy of Sciences · 2004 · 95 citations · 29 references
Life SciencesBiochemistryMolecular BiologyCell SignalingEnzymologyMolecular Cell BiologyCell Membrane StructureEndomembrane SystemMembrane DomainsMembrane OrganizationMembrane Protein TopologyProtein-lipid Interactions5-Lipoxygenase ActivationLeukotriene BiosynthesisLeukotriene PathwaysLeukotriene ProductionLeukotriene SignalingMembrane Domain OrganizationOrganelle Membrane OrganizationOuter Nuclear Membrane Proteins
Cell signaling leading to the formation of leukotriene (LT)C(4) requires the localization of the four key biosynthetic enzymes on the outer nuclear membrane and endoplasmic reticulum. Whether any macromolecular organization of these proteins exists is unknown. By using fluorescence lifetime imaging microscopy and biochemical analysis, we demonstrate the presence of two distinct multimeric complexes that regulate the formation of LTs in RBL-2H3 cells. One complex consists of multimers of LTC(4) synthase and the 5-lipoxygenase activating protein (FLAP). The second complex consists of multimers of FLAP. Surprisingly, all LTC(4) synthase was found to be in association with FLAP. The results indicate that the formation of LTC(4) and LTB(4) may be determined by the compartmentalization of biosynthetic enzymes in discrete molecular complexes.
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Requirement of a 5-lipoxygenase-activating protein for leukotriene synthesis
Richard A. F. Dixon, Ronald E. Diehl, Evan E. Opas et al. · Nature · 1990 · 776 citations