ArticleProceedings of the National Academy of Sciences of the United States of America2000
5-lipoxygenase is phosphorylated by p38 kinase-dependent MAPKAP kinases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 218 citations in OpenAlex.
- A mechanism of benefit of soy genistein in asthma: inhibition of eosinophil p38-dependent leukotriene synthesis.Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2008Trial
- Article
- Embelin Mitigates the Impact of Perinatal Inflammation on Neuron Development by Inhibiting 5-Lipoxygenase-Mediated Ferroptosis.Phytotherapy research : PTR · 2025Article
- Distinct mechanisms of type 3 secretion system recognition control LTB4 synthesis in neutrophils and macrophages.PLoS pathogens · 2024Article
- Distinct Mechanisms of Type 3 Secretion System Recognition Control LTBbioRxiv : the preprint server for biology · 2024Article
- Article
- A critical role for Macrophage-derived Cysteinyl-Leukotrienes in HIV-1 induced neuronal injury.Brain, behavior, and immunity · 2024Article
- Formyl Peptide Receptor 2-Dependent cPLA2 and 5-LOX Activation Requires a Functional NADPH Oxidase.Antioxidants (Basel, Switzerland) · 2024Article
- Mitogen-activated protein kinase-activated protein kinase-2 (MK2) and its role in cell survival, inflammatory signaling, and migration in promoting cancer.Molecular carcinogenesis · 2022Article
- Mitochondria-targeted antioxidant SkQ1 inhibits leukotriene synthesis in human neutrophils.Frontiers in pharmacology · 2022Article
- Mechanistic insight on the role of leukotriene receptors in ischemic-reperfusion injury.Pharmacological reports : PR · 2021Review
- Candida albicans-induced leukotriene biosynthesis in neutrophils is restricted to the hyphal morphology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- miRNAs and Leukotrienes in Respiratory Syncytial Virus Infection.Frontiers in pediatrics · 2021Review
- Communication between human macrophages and epithelial cancer cell lines dictates lipid mediator biosynthesis.Cellular and molecular life sciences : CMLS · 2020Article
- Exotoxins from Staphylococcus aureus activate 5-lipoxygenase and induce leukotriene biosynthesis.Cellular and molecular life sciences : CMLS · 2020Article
- Phosphorylation of 5-LOX: The Potential Set-point of Inflammation.Neurochemical research · 2020Review
- Redundant and Cooperative Roles for Yersinia pestis Yop Effectors in the Inhibition of Human Neutrophil Exocytic Responses Revealed by Gain-of-Function Approach.Infection and immunity · 2020Article
- Article
- Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities.Nature reviews. Cardiology · 2019Review
- Emerging Roles of 5-Lipoxygenase Phosphorylation in Inflammation and Cell Death.Oxidative medicine and cellular longevity · 2019Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
5-lipoxygenase (5-LO) catalyzes the initial steps in the formation of leukotrienes, a group of inflammatory mediators derived from arachidonic acid (AA). Here we describe that activation of p38 mitogen-activated protein kinase in human polymorphonuclear leukocytes and in Mono Mac 6 cells leads to activation of downstream kinases, which can subsequently phosphorylate 5-LO in vitro. Different agents activated the 5-LO kinase activities, including stimuli for cellular leukotriene biosynthesis (A23187, thapsigargin, N-formyl-leucyl-phenylalanine), compounds that up-regulate the capacity for leukotriene biosynthesis (phorbol 12-myristate 13-acetate, tumor necrosis factor alpha, granulocyte/macrophage colony-stimulating factor), and well known p38 stimuli as sodium arsenite and sorbitol. For all stimuli, 5-LO kinase activation was counteracted by SB203580 (3 microM or less), an inhibitor of p38 kinase. At least two p38-dependent 5-LO kinase activities were found. Based on migration properties in in-gel kinase assays and immunoreactivity, one of these was identified as mitogen-activated protein kinase-activated protein kinase 2 (MAPKAP kinase 2). The other appeared to be MAPKAP kinase 3; however, it could not be excluded that also other p38-dependent kinases contributed. When polymorphonuclear leukocytes were incubated with sodium arsenite (strong activator of 5-LO kinases), platelet-activating factor and exogenous AA, there was a 4-fold increase in 5-LO activity as compared with incubations with only platelet-activating factor and AA. This indicates that 5-LO phosphorylation can be one factor determining cellular 5-LO activity.
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