ArticleMolecular biology of the cell2012
The nuclear membrane leukotriene synthetic complex is a signal integrator and transducer.
Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 36 citations in OpenAlex.
- Microglial 5-LOX-activating protein antagonism alleviates leukotriene-driven neuroinflammation.Acta neuropathologica · 2026Article
- Mitochondria-targeted antioxidant SkQ1 inhibits leukotriene synthesis in human neutrophils.Frontiers in pharmacology · 2022Article
- Untangling the web of 5-lipoxygenase-derived products from a molecular and structural perspective: The battle between pro- and anti-inflammatory lipid mediators.Biochemical pharmacology · 2021Review
- Sex Hormones and Lung Inflammation.Advances in experimental medicine and biology · 2021Article
- Gram-Negative BacteriaFrontiers in pharmacology · 2021Article
- Phosphorylation of 5-LOX: The Potential Set-point of Inflammation.Neurochemical research · 2020Review
- Two- and three-color STORM analysis reveals higher-order assembly of leukotriene synthetic complexes on the nuclear envelope of murine neutrophils.The Journal of biological chemistry · 2020Article
- Article
- A 5‑lipoxygenase-specific sequence motif impedes enzyme activity and confers dependence on a partner protein.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Article
- Article
- Alisol B 23-Acetate Inhibits IgE/Ag-Mediated Mast Cell Activation and Allergic Reaction.International journal of molecular sciences · 2018Article
- Cis interaction between sialylated FcγRIIA and the αI-domain of Mac-1 limits antibody-mediated neutrophil recruitment.Nature communications · 2018Article
- Neutrophil-Derived Cytosolic PLA2α Contributes to Bacterial-Induced Neutrophil Transepithelial Migration.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- The anti-inflammatory effects of Yunnan Baiyao are involved in regulation of the phospholipase A2/arachidonic acid metabolites pathways in acute inflammation rat model.Molecular medicine reports · 2017Article
- Androgen-mediated sex bias impairs efficiency of leukotriene biosynthesis inhibitors in males.The Journal of clinical investigation · 2017Article
- 5-Lipoxygenase-activating protein rescues activity of 5-lipoxygenase mutations that delay nuclear membrane association and disrupt product formation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Cytosolic phospholipase A₂: physiological function and role in disease.Journal of lipid research · 2015Review
- Article
- Roles of coactosin-like protein (CLP) and 5-lipoxygenase-activating protein (FLAP) in cellular leukotriene biosynthesis.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- The novel benzimidazole derivative BRP-7 inhibits leukotriene biosynthesis in vitro and in vivo by targeting 5-lipoxygenase-activating protein (FLAP).British journal of pharmacology · 2014Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Leukotrienes (LTs) are lipid-signaling molecules derived from arachidonic acid (AA) that initiate and amplify inflammation. To initiate LT formation, the 5-lipoxygenase (5-LO) enzyme translocates to nuclear membranes, where it associates with its scaffold protein, 5-lipoxygenase-activating protein (FLAP), to form the core of the multiprotein LT synthetic complex. FLAP is considered to function by binding free AA and facilitating its use as a substrate by 5-LO to form the initial LT, LTA(4). We used a combination of fluorescence lifetime imaging microscopy, cell biology, and biochemistry to identify discrete AA-dependent and AA-independent steps that occur on nuclear membranes to control the assembly of the LT synthetic complex in polymorphonuclear leukocytes. The association of AA with FLAP changes the configuration of the scaffold protein, enhances recruitment of membrane-associated 5-LO to form complexes with FLAP, and controls the closeness of this association. Granulocyte monocyte colony-stimulating factor provides a second AA-independent signal that controls the closeness of 5-LO and FLAP within complexes but not the number of complexes that are assembled. Our results demonstrate that the LT synthetic complex is a signal integrator that transduces extracellular signals to modulate the interaction of 5-LO and FLAP.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.