ArticleProceedings of the National Academy of Sciences of the United States of America2011
15-Lipoxygenase 1 interacts with phosphatidylethanolamine-binding protein to regulate MAPK signaling in human airway epithelial cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 1 of them a synthesis that pooled it.
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Who cites it
84 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- Review of ferroptosis in colorectal cancer: Friends or foes?World journal of gastroenterology · 2023Pooled it
- Novel keto-phospholipids are generated by monocytes and macrophages, detected in cystic fibrosis, and activate peroxisome proliferator-activated receptor-γ.The Journal of biological chemistry · 2012Trial
- Aberrant mucin expression and keratinization distinguishing severe from mild asthma revealed by interpretable machine learning.JCI insight · 2026Article
- ALOX15 orchestrates mitochondrial antiviral immunity and serves as a host target for anti-influenza therapy.Nature immunology · 2026Article
- 15-LOX-catalytic bias towards ether-(alkenyl)-ETE-PEs oxidation bestows selectivity of PRO-ferroptotic cell death signaling.Nature communications · 2026Article
- Spatial transcriptomics reveals coordinated endothelial and epithelial activator protein-1 activation in chronic lung allograft dysfunction.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2026Article
- Convergent death programs in chronic obstructive pulmonary disease: how pyroptotic and ferroptotic crosstalk reshapes therapeutic paradigms.Frontiers in immunology · 2026Review
- Identification and Validation of ALOX15 as a Robust Diagnostic Biomarker for Obesity-Associated Asthma: An Integrative Bioinformatic and Experimental Study.Journal of inflammation research · 2026Article
- The role of ALOX15 in inflammation-related diseases.Frontiers in immunology · 2026Review
- The YYR (YY1- RKIP) Regulatory Axis in the pathogenesis of Cancer and Immune Evasion.Journal of experimental & clinical cancer research : CR · 2025Review
- Targeting IL-4/IL-13 Signaling Pathways in Chronic Rhinosinusitis with Nasal Polyps: From Mechanisms to Therapies.Clinical reviews in allergy & immunology · 2025Review
- KRAS/ABHD17C/ALOX15B Axis Promotes Pancreatic Cancer Progression via Ferroptosis Evasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The Evolution of Fluorescein into A Potential Theranostic Tool.Chemistry (Weinheim an der Bergstrasse, Germany) · 2025Article
- Predictive significance of 15(S)-hydroxyeicosatetraenoic acid for eosinophilic chronic rhinosinusitis with nasal polyps.Asia Pacific allergy · 2025Article
- PEBP1 and 15-LO-1 in Asthma: Biomarker Potential for Diagnosis and Severity Stratification.Diagnostics (Basel, Switzerland) · 2025Article
- Cell death crosstalk in respiratory diseases: unveiling the relationship between pyroptosis and ferroptosis in asthma and COPD.Molecular and cellular biochemistry · 2025Review
- Crafting Molecular Tools for 15-Lipoxygenase-1 in a Single Step.Angewandte Chemie (International ed. in English) · 2025Article
- Aspirin hypersensitivity diagnostic index (AHDI): In vitro test for diagnosing of N-ERD based on urinary 15-oxo-ETE and LTEAllergy · 2025Article
- PCYT2 inhibits epithelial-mesenchymal transition in colorectal cancer by elevating YAP1 phosphorylation.JCI insight · 2024Article
- Compartmentalized mitochondrial ferroptosis converges with optineurin-mediated mitophagy to impact airway epithelial cell phenotypes and asthma outcomes.Nature communications · 2024Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Epithelial 15-lipoxygenase 1 (15LO1) and activated ERK are increased in asthma despite modest elevations in IL-13. MAPK kinase (MEK)/ERK activation is regulated by interactions of Raf-1 with phosphatidylethanolamine-binding protein 1 (PEBP1). Epithelial 15LO1 generates intracellular 15-hydroxyeicosatetraenoic acid (15HETE) conjugated to phosphatidylethanolamine (PE) (15HETE-PE). We hypothesized that (i) 15LO1 and its product 15HETE-PE serve as signaling molecules interacting with PEBP1 to activate Raf-1/MEK/ERK and that (ii) this 15LO1-15HETE-PE-regulated ERK activation amplifies IL-4Rα downstream pathways. Our results demonstrate that high epithelial 15LO1 levels correlate with ERK phosphorylation ex vivo. In vitro, IL-13 induces 15LO1, which preferentially binds to PEBP1, causing PEBP1 to dissociate from Raf-1 and activate ERK. Exogenous 15HETE-PE similarly induces dissociation of PEBP1 from Raf-1 independently of IL-13/15LO1. siRNA knockdown of 15LO1 decreases the dissociation of Raf-1 from PEBP1, and the resulting lower ERK activation leads to lower downstream IL-4Rα-related gene expression. Identical protein-protein interactions are observed in endobronchial biopsies and fresh epithelial cells from asthmatics ex vivo. Colocalization of Raf-1 to PEBP1 is low in asthmatic tissue and cells compared with normals, whereas there is striking colocalization of 15LO1 with PEBP1 in asthma. Low 15LO1 levels in normals limit its colocalization with PEBP1. The results confirm a previously unknown signaling role for 15LO1 and its PE-conjugated eicosanoid product in human airway epithelial cells. This pathway enhances critical inflammatory pathways integral to asthma pathogenesis.
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