ArticleProceedings of the National Academy of Sciences of the United States of America2013
Ligand-specific conformational change of the G-protein-coupled receptor ALX/FPR2 determines proresolving functional responses.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 202 papers.
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Who cites it
202 citing papers in PubMed, 293 citations in OpenAlex.
- Lipoxins modulate neutrophil oxidative burst, integrin expression and lymphatic transmigration differentially in human health and atherosclerosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Trial
- GABA ameliorates diabetic kidney disease-induced podocyte injury via JAML-FPR2 axis-mediated suppression of macrophage infiltration.Renal failure · 2026Article
- Stem cells redirect the neuroinflammatory trajectory of primed microglia in an ovine chorioamnionitis model.Brain, behavior, & immunity - health · 2026Article
- Synthetic FLS2 receptor oligomer boosts plant innate immunity.Science advances · 2026Article
- Targeted Delivery of Specialized Pro-Resolving Mediators (SPMs) for Improved Treatments of Inflammatory Diseases and Cancer.Pharmaceutics · 2026Review
- The Role of Immunoresolvents in Atherosclerosis: A Mini-Review on Their Biology and Therapeutic Opportunities.Health science reports · 2026Article
- FPR2 deficiency alleviates LPS-induced depressive-like behaviors in mice by suppressing the microglial CSF1/NLRP3 inflammasome pathway.Journal of neuroinflammation · 2026Article
- Toward a Therapy for Autism Spectrum Disorder: The Formyl Peptide Receptor 2 Agonist MR-39 Supports Synaptic Health in the BTBR Mouse and Features a Favorable Safety Profile.ACS pharmacology & translational science · 2026Article
- G protein-coupled receptors and inflammation resolution signaling networks in the heart: Pharmacology and potential for innovative therapeutics.Pharmacological reviews · 2026Review
- LAT1/SLC7A5-mediated amino acid uptake is regulated by redox signals triggered by formyl-peptide receptor 2.The FEBS journal · 2026Article
- Macrophage plasticity and metabolic control in muscle repair and disease.Frontiers in immunology · 2026Review
- Specialized pro-resolving mediators and cancer: news and promises from the other side of the moon.Frontiers in pharmacology · 2026Review
- Inflammation-resolution signalling in cardiac repair, remodelling, and heart failure.European heart journal open · 2025Review
- Annexin A1 as a key modulator of lung inflammation during coronavirus infections.Clinical science (London, England : 1979) · 2025Article
- Genetic deletion of Alx/Fpr2 differentially regulates pulmonary inflammation in the absence and presence of acute lung injury.ImmunoHorizons · 2025Article
- FPR2 Agonism Attenuates Restenosis by Mitigating Neointimal Hyperplasia via ELOVL6.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Design, Synthesis, and Biological Evaluation of Novel Heteroaryl, Squaramide, and Indolcarboxamide Derivatives as Formyl Peptide Receptor 2 Agonists to Target Neuroinflammation.ACS chemical neuroscience · 2025Article
- Lipoxins as Modulators of Diseases.Cells · 2025Review
- ALX/FPR2 Receptor Activation by Inflammatory (fMLFII) and Pro-resolving (LXAACS physical chemistry Au · 2025Article
- Oral FPR2/ALX modulators tune myeloid cell activity to ameliorate mucosal inflammation in inflammatory bowel disease.Acta pharmacologica Sinica · 2025Article
142 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Formyl-peptide receptor type 2 (FPR2), also called ALX (the lipoxin A4 receptor), conveys the proresolving properties of lipoxin A4 and annexin A1 (AnxA1) and the proinflammatory signals elicited by serum amyloid protein A and cathelicidins, among others. We tested here the hypothesis that ALX might exist as homo- or heterodimer with FPR1 or FPR3 (the two other family members) and operate in a ligand-biased fashion. Coimmunoprecipitation and bioluminescence resonance energy transfer assays with transfected HEK293 cells revealed constitutive dimerization of the receptors; significantly, AnxA1, but not serum amyloid protein A, could activate ALX homodimers. A p38/MAPK-activated protein kinase/heat shock protein 27 signaling signature was unveiled after AnxA1 application, leading to generation of IL-10, as measured in vitro (in primary monocytes) and in vivo (after i.p. injection in the mouse). The latter response was absent in mice lacking the ALX ortholog. Using a similar approach, ALX/FPR1 heterodimerization evoked using the panagonist peptide Ac2-26, identified a JNK-mediated proapoptotic path that was confirmed in primary neutrophils. These findings provide a molecular mechanism that accounts for the dual nature of ALX and indicate that agonist binding and dimerization state contribute to the conformational landscape of FPRs.
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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.