Affinage

FPR2

N-formyl peptide receptor 2 · UniProt P25090

Length
351 aa
Mass
39.0 kDa
Annotated
2026-04-28
100 papers in source corpus 35 papers cited in narrative 35 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FPR2/ALX is a promiscuous Gi-coupled G-protein-coupled receptor that integrates structurally diverse ligands — including lipoxin A4, annexin A1, resolvin D1, serum amyloid A, amyloid β42, long-chain ceramides, uPAR fragments, and bacterial peptides — to drive ligand-biased signaling controlling neutrophil chemotaxis, NADPH oxidase activation, macrophage efferocytosis, and inflammatory resolution (PMID:11818541, PMID:12393391, PMID:40080544, PMID:20570963). Ligand identity determines receptor dimer configuration (homodimers versus FPR1/FPR3 heterodimers) and selects among Gi-cAMP, PLC-calcium-PKC, p38/ERK MAPK, PI3K/Akt, AMPK/mTOR, and β-arrestin-dependent pathways; β-arrestin recruitment is specifically required for chemotaxis but dispensable for NADPH oxidase activation, and a C-terminal tail recycling sequence governs whether receptor internalization leads to resensitization or apoptotic signaling (PMID:24108355, PMID:28855087, PMID:25326384, PMID:31694908). Cryo-EM structures reveal a polar intrabundle cavity and a hydrophobic extracellular groove that together accommodate peptide, lipid, and ceramide agonists in the orthosteric pocket, while chimeric receptor studies map ligand-selective determinants to the N-terminus and extracellular loops I–II (PMID:35365641, PMID:40080544, PMID:22610094). In myeloid cells in vivo, FPR2 is non-redundantly required for pro-resolving macrophage polarization, efferocytosis, revascularization after ischemia, and protection from sepsis-induced organ dysfunction (PMID:25512512, PMID:32513697, PMID:36628837, PMID:30862681).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 High

    Establishing that FPR2 functions as a low-affinity formyl peptide receptor on neutrophils with distinct chemotactic properties from FPR1 resolved the question of whether multiple formyl peptide receptor subtypes mediate biphasic neutrophil chemotaxis.

    Evidence HEK293 transfectants and FPR-knockout mouse neutrophils with calcium flux and chemotaxis assays

    PMID:10477558

    Open questions at the time
    • Human FPR2-specific knockout not yet available at this stage
    • Endogenous ligand hierarchy not addressed
  2. 2000 High

    Identification of serum amyloid A and HIV gp120-derived peptides as FPR2 agonists revealed that the receptor accepts structurally diverse ligands beyond formyl peptides, establishing its promiscuous ligand recognition.

    Evidence FPR2- versus FPR-transfected HEK293 cells, cross-desensitization, calcium flux, chemotaxis; FPR-knockout mouse neutrophils

    PMID:10438703 PMID:10753626

    Open questions at the time
    • Structural basis of promiscuity unknown
    • No competition binding with lipid ligands yet tested
  3. 2002 High

    Discovery that uPAR cleavage products and SAA activate FPR2 to induce NF-κB/ERK/p38/calcium signaling linked the receptor to both the fibrinolytic system and acute-phase inflammation, broadening its physiological scope beyond chemotaxis.

    Evidence Competition binding, antibody blockade, pertussis toxin, NF-κB reporters in THP-1/HeLa/monocytes

    PMID:11818541 PMID:12393391

    Open questions at the time
    • Whether different agonists engage distinct intracellular pathways not yet systematically compared
    • TNFα-driven transcriptional regulation of FPR2 only shown in microglia
  4. 2010 High

    Demonstration that PKC-dependent FPR2 internalization is required for LXA4/Ac2-26-stimulated macrophage phagocytosis of apoptotic neutrophils, validated in Fpr2-knockout mice, established receptor trafficking as a determinant of efferocytosis.

    Evidence HA-tagged FPR2 trafficking by confocal/immunogold, Fpr2−/− bone marrow macrophages, phagocytosis assays

    PMID:20570963

    Open questions at the time
    • Role of β-arrestin in this trafficking step not yet dissected
    • Receptor recycling fate not characterized
  5. 2012 High

    Chimeric FPR1/FPR2 domain-swap experiments mapped ligand-selective determinants — the N-terminus for AnxA1, extracellular loops I–II for SAA, and loop I/TM2 for small molecules — answering how a single receptor discriminates structurally diverse agonists.

    Evidence Stable HEK293 chimeric receptor transfectants with genomic response and desensitization analysis

    PMID:22610094

    Open questions at the time
    • Atomic-resolution contacts not available
    • Whether dimerization state influences ligand selectivity not addressed
  6. 2013 High

    BRET and co-IP evidence that FPR2 constitutively forms homo- and heterodimers with FPR1/FPR3, with dimer composition dictating pro-resolving (p38/IL-10) versus pro-apoptotic (JNK) signaling, introduced receptor oligomerization as the structural basis for ligand bias.

    Evidence BRET and co-IP in HEK293 cells, FPR2-knockout mouse validation, pathway analysis

    PMID:24108355

    Open questions at the time
    • Stoichiometry and dynamics of dimers in native cells unknown
    • Whether all ligands have defined dimer preferences not tested
  7. 2014 High

    A cluster of studies established that a C-terminal recycling sequence controls receptor resensitization versus apoptosis, that miR-181b post-transcriptionally regulates FPR2 during macrophage differentiation, that Sp1/DNA methylation governs basal transcription, and that Fpr2/3-knockout mice suffer exacerbated sepsis — collectively defining FPR2 regulation at transcriptional, post-transcriptional, and trafficking levels and its non-redundant role in vivo.

    Evidence C-tail mutagenesis/apoptosis assays; miR-181b 3′-UTR reporter/phagocytosis; Sp1 ChIP/promoter SNP; CLP sepsis in Fpr2/3−/− mice with echocardiography

    PMID:22131270 PMID:25326384 PMID:25505240 PMID:25512512

    Open questions at the time
    • How recycling sequence interacts with sorting machinery unresolved
    • Whether miR-181b regulation applies in neutrophils not tested
    • Functional consequence of the Sp1-site SNP on disease susceptibility not established in cohort studies
  8. 2017 High

    The pepducin F2Pal10 demonstrated that β-arrestin recruitment is specifically required for FPR2-mediated chemotaxis but dispensable for PLC-calcium and NADPH oxidase activation, formally dissecting biased signaling at this receptor.

    Evidence Pepducin pharmacology in primary human neutrophils with β-arrestin recruitment, calcium, oxidase, and chemotaxis assays

    PMID:28855087

    Open questions at the time
    • Structural basis of β-arrestin-biased versus G-protein-biased activation unknown
    • Whether this bias operates identically in macrophages not shown
  9. 2019 High

    Structure-activity analysis of bacterial PSMα peptides identified the N-terminal and C-terminal residues as determinants for β-arrestin recruitment versus G-protein signaling, and the AnxA1/FPR2 axis was shown to regulate platelet Akt/Rap1 signaling to control integrin activation and thrombus formation.

    Evidence PSMα2 SAR with primary neutrophils; AnxA1−/− mice with intravital microscopy and human platelet assays

    PMID:31154815 PMID:31694908

    Open questions at the time
    • Whether PSMα-FPR2 binding mode differs from endogenous ligands structurally not resolved
    • Platelet-specific FPR2 deletion not performed
  10. 2020 High

    Multiple studies revealed that FPR2 endocytosis can occur independently of β-arrestin (via AP2), that FPR2 interacts with TAK1 to modulate NF-κB in macrophages, that myeloid FPR2 drives SAA3-mediated adipose inflammation, and that myeloid-specific deletion impairs ischemia-driven revascularization — extending FPR2's non-redundant roles to metabolic inflammation and tissue repair.

    Evidence β-arrestin-deficient cells with Barbadin; Fpr2-KO co-IP for TAK1; myeloid-specific Fpr2-KO bone marrow transplant on HFD; myeloid Fpr2-KO hindlimb ischemia with RNA-seq

    PMID:30862681 PMID:32106380 PMID:32513697 PMID:32916203

    Open questions at the time
    • TAK1 interaction confirmed by co-IP only; reciprocal pull-down or structural validation lacking
    • Whether AP2-mediated endocytosis engages distinct signaling versus β-arrestin route unknown
    • Transcriptional targets mediating revascularization not fully validated
  11. 2022 High

    Cryo-EM structures of FPR2-Gi complexes with Aβ42 and fHN revealed the bipartite binding mode (polar intrabundle cavity plus hydrophobic extracellular groove) and structural differences from FPR1 that explain ligand selectivity, providing the first atomic framework for this receptor.

    Evidence Cryo-EM structure determination with mutagenesis and G-protein/β-arrestin functional assays

    PMID:35365641

    Open questions at the time
    • No structures with pro-resolving lipid agonists (LXA4, RvD1) available
    • Heterodimer structures not solved
  12. 2023 High

    Identification of columbamine as a biased FPR2 agonist that promotes LC3-associated phagocytosis (LAP)-mediated efferocytosis, abolished by Fpr2 genetic ablation, linked FPR2 to autophagy-associated phagocytic clearance in intestinal inflammation.

    Evidence Fpr2-KO mice, FPR2 antagonism, colitis model, LAP autophagy assays, transcriptome analysis

    PMID:37994307

    Open questions at the time
    • Whether LAP induction is unique to biased agonists or a general FPR2 function unknown
    • Direct binding mode of columbamine not structurally resolved
  13. 2025 High

    Cryo-EM structures of FPR2-Gi with C16–C20 ceramides demonstrated that FPR2 serves as a bona fide lipid receptor with ceramide tails embedded in the orthosteric pocket, and FPR2-KO adipocytes confirmed that ceramide-FPR2-Gi-cAMP signaling suppresses thermogenesis, revealing a metabolic function.

    Evidence Three cryo-EM structures, Gi-cAMP signaling assays, FPR2-KO adipocyte studies

    PMID:40080544

    Open questions at the time
    • Whether ceramide-FPR2 signaling is relevant in immune cells unknown
    • Ceramide versus LXA4 competition at the orthosteric site not tested
    • In vivo metabolic phenotype of adipocyte-specific Fpr2 deletion not reported

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: how heterodimer structures accommodate different ligand classes, whether lipid (LXA4/RvD1) and ceramide agonists compete at the orthosteric pocket, how β-arrestin-biased versus G-protein-biased conformations differ structurally, and what determines cell-type-specific signaling outcomes (pro-inflammatory in adipose macrophages versus pro-resolving in lung macrophages).
  • No heterodimer cryo-EM structures
  • No structures with LXA4 or RvD1 bound
  • Cell-type determinants of signaling bias uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5 GO:0008289 lipid binding 1
Localization
GO:0005886 plasma membrane 5
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-168256 Immune System 5 R-HSA-1430728 Metabolism 3
Partners
ANXA1ARRB1ARRB2FPR1FPR3MAP3K7SAA1
Complex memberships
FPR2 homodimerFPR2/FPR1 heterodimerFPR2/FPR3 heterodimer

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 A cleaved soluble form of urokinase plasminogen activator receptor (uPAR), D2D3(88-274), directly binds to FPRL1/FPR2 and induces chemotaxis; this interaction was blocked by specific FPR2 antibodies and agonists, establishing uPAR as an endogenous chemotactic agonist for FPR2 and linking the fibrinolytic pathway to FPR2-mediated cell migration. Direct binding assay (competition with MMK-1 and LXA4 analogue), antibody inhibition, receptor desensitization experiments, THP-1 cells and human monocytes Proceedings of the National Academy of Sciences of the United States of America High 11818541
2002 Serum amyloid A (SAA) activates FPR2/FPRL1 (a Gi-coupled receptor) to induce IL-8 secretion via NF-κB activation, calcium mobilization, and ERK1/2/p38 MAPK signaling; pertussis toxin blockade and anti-FPR2 N-terminal antibody confirmed receptor involvement. Pertussis toxin inhibition, FPR2 overexpression in HeLa cells, luciferase reporters, anti-FPR2 antibody blockade, calcium mobilization assays Blood High 12393391
1999 A synthetic peptide (F peptide) from HIV-1 gp120 (aa 414-434) uses FPR2/FPRL1 as a functional receptor, inducing chemotaxis and calcium mobilization in monocytes/neutrophils, and leading to PKC-dependent downregulation of CCR5 and CXCR4 surface expression. Transfection of HEK cells with FPR2 cDNA, calcium mobilization, cross-desensitization experiments, flow cytometry Blood High 10438703
2013 FPR2/ALX constitutively forms homodimers and heterodimers with FPR1 or FPR3 as shown by co-immunoprecipitation and BRET assays; ligand bias determines signaling: AnxA1 activates ALX homodimers via p38/MAPK/HSP27/IL-10 pathway, while panagonist Ac2-26 on ALX/FPR1 heterodimers evokes a JNK-mediated pro-apoptotic pathway. Co-immunoprecipitation, bioluminescence resonance energy transfer (BRET) in HEK293 cells, signaling pathway analysis, FPR2-knockout mouse validation Proceedings of the National Academy of Sciences of the United States of America High 24108355
2010 FPR2/ALX undergoes PKC-dependent internalization upon stimulation by LXA4 or Ac2-26, and this internalization is required for phagocytosis of apoptotic neutrophils; bone marrow-derived macrophages from Fpr2-knockout mice fail to respond to LXA4 or Ac2-26 in phagocytosis assays. HA-tagged FPR2 trafficking by confocal microscopy, immunogold labeling, ELISA; bone marrow macrophages from Fpr2-/- mice; phagocytosis assays FASEB journal High 20570963
2012 The N-terminal region and extracellular loop II of FPR2/ALX are required for AnxA1-mediated signaling (including JAG1/JAM3 induction), while extracellular loops I and II mediate SAA responses, and the small molecule compound 43 signals through extracellular loop I/transmembrane region II; identified using chimeric FPR1/FPR2 clones stably transfected in HEK293 cells. Chimeric receptor domain-swap clones stably transfected in HEK293 cells, genomic response analysis, desensitization experiments The Journal of biological chemistry High 22610094
1999 Mouse FPR2 (encoded by Fpr-rs2) is a functional N-formylpeptide receptor subtype expressed selectively on neutrophils; fMLF induces two distinct concentration optima for chemotaxis via high-affinity FPR and low-affinity FPR2, demonstrated using FPR-knockout mice and HEK293 transfectants. Stable transfection of HEK293 cells, calcium flux assays, chemotaxis assays, FPR-knockout mice The Journal of experimental medicine High 10477558
2000 Serum amyloid A (SAA) is a specific chemotactic agonist for mouse FPR2 (counterpart of human FPRL1R); SAA selectively induced calcium flux and chemotaxis in HEK293/FPR2 transfectants but not in FPR-transfected cells, and fMLF desensitized SAA responses in both mouse neutrophils and FPR2 transfectants. HEK293 cell transfection with FPR2 or FPR, calcium flux, chemotaxis, cross-desensitization, FPR+/+ vs FPR-/- mice Biochemical and biophysical research communications High 10753626
2007 F2L (acetylated heme-binding protein-derived peptide) specifically activates mouse Fpr2 with EC50 ~400-500 nM in calcium flux, cAMP inhibition, and chemotaxis assays; neutrophils from Fpr2-deficient mice fail to respond to F2L, confirming Fpr2 as the exclusive mouse receptor for F2L. Transfection of cell lines with all 8 mouse Fpr receptor cDNAs, calcium flux, cAMP inhibition, chemotaxis; Fpr2-/- mouse neutrophils Journal of immunology High 17237393
2014 FPR2/ALX mediates LPS-induced IL-8 secretion and receptor internalization in neutrophils following SAA stimulation; SAA can allosterically modify FPR2 so it no longer transduces pro-resolving signals from lipoxins. Pharmacological receptor studies, in vitro signaling assays Pharmacology & therapeutics Medium 23880288
2014 Cathelin-related antimicrobial peptide (CRAMP), an endogenous FPR2 ligand expressed by dendritic cells (DCs), is required for normal DC maturation upon LPS stimulation; neutralization of Fpr2 or CRAMP inhibits DC maturation, CCL21-mediated chemotaxis, and allogeneic T-cell proliferation. Fpr2-/- and CRAMP-/- mouse bone marrow DCs, LPS stimulation, neutralizing antibodies, co-culture allogeneic T-cell assays, in vivo immunization The Journal of biological chemistry High 24808174
2017 FPR2 signals in a β-arrestin-biased versus unbiased fashion: the pepducin F2Pal10 activates PLC-PIP2-Ca2+ signaling and NADPH-oxidase but fails to recruit β-arrestin; lack of β-arrestin recruitment leads to reduced receptor internalization rate and impaired chemotaxis, demonstrating that β-arrestin is required for FPR2-mediated neutrophil migration. Pepducin pharmacology in human neutrophils, β-arrestin recruitment assay, calcium flux, NADPH-oxidase assay, chemotaxis assay, receptor desensitization Biochemical pharmacology High 28855087
2014 FPR2/ALX undergoes β-arrestin-mediated endocytosis followed by rapid recycling to the plasma membrane; a transplantable recycling sequence in the C-terminal tail was identified that is necessary and sufficient for recycling; removal of this sequence shifts receptor fate toward apoptotic signaling upon agonist activation. C-terminal truncation/mutagenesis, receptor trafficking assays, apoptosis assays in transfected cells The Journal of biological chemistry High 25326384
2019 Staphylococcus aureus PSMα peptides activate FPR2 in neutrophils (calcium flux, NADPH-oxidase, ERK1/2 phosphorylation, internalization) but lack the ability to recruit β-arrestin and induce chemotaxis; structure-activity analysis identified the first 3 aa and C-terminus of PSMα2 as critical for β-arrestin recruitment, linking β-arrestin to chemotactic signaling. Primary neutrophil functional assays, β-arrestin recruitment assay, SAR with PSMα2 derivatives, ERK1/2 phosphorylation, NADPH-oxidase Journal of immunology High 31694908
2020 FPR2 endocytosis occurs independently of β-arrestin (demonstrated in β-arrestin-deficient cells), though β-arrestin contributes; the AP2/β-arrestin interaction inhibitor Barbadin potentiates FPR2-mediated ROS production independently of receptor endocytosis, implicating AP2 in FPR2-mediated ROS release. β-arrestin-deficient cell lines, Barbadin inhibitor, NADPH-oxidase assay, chemotaxis assay, FPR2 endocytosis tracking Biochimica et biophysica acta. Molecular cell research High 32916203
2022 Cryo-EM structures of FPR2 in complex with Gi and Aβ42 or N-formyl humanin (fHN) revealed two critical binding regions: a polar cavity within the receptor helical bundle and a hydrophobic groove in the extracellular region that govern ligand recognition and activity; structural comparison with FPR1 provided insights into ligand selectivity. Cryo-EM structure determination, functional assays (G-protein activation, β-arrestin recruitment), mutagenesis Nature communications High 35365641
2025 FPR2 was identified as a membrane receptor that specifically binds long-chain ceramides (C14-C20); cryo-EM structures of FPR2-Gi complexes with C16:0, C18:0, and C20:0 ceramides show the hydrophobic tails embedded in the orthosteric pocket; in brown/beige adipocytes, C16:0 ceramide binding to FPR2 inhibits thermogenesis via Gi-cAMP signaling. Cryo-EM structural determination (3 structures), functional Gi-cAMP signaling assays, FPR2-knockout adipocyte studies, ceramide binding experiments Science High 40080544
2014 Fpr2/3-knockout mice show exacerbated sepsis severity (hypothermia, cardiac dysfunction, altered cytokine profiles, reduced monocyte recruitment) and TNFα drives over-threefold increase in Fpr2/3 promoter activity in granulocytes and monocytes post-CLP; peptido-agonist treatment protected wild-type but not Fpr2/3-/- mice from myocardial dysfunction, demonstrating non-redundant modulatory role. Caecal ligation and puncture (CLP) in Fpr2/3-/- mice, GFP reporter for promoter activity, echocardiography, cytokine quantification, flow cytometry Proceedings of the National Academy of Sciences of the United States of America High 25512512
2011 Sp1 binds the FPR2/ALX core promoter (confirmed by ChIP), is required for maximal promoter activity, and DNA methylation suppresses promoter activity; LXA4 enhances FPR2 promoter activity and mRNA expression; a heritable SNP in the Sp1 site reduces promoter activity by 35-90% and reduces FPR2 mRNA/protein in carrier neutrophils. Chromatin immunoprecipitation (ChIP), site-directed mutagenesis, Sp1 overexpression, luciferase reporter, methylation analysis, patient neutrophil qPCR/Western blot FASEB journal High 22131270
2014 MicroRNA-181b directly binds the 3'-UTR of FPR2/ALX mRNA (validated by luciferase reporter) and downregulates FPR2 protein; miR-181b levels decrease during monocyte-to-macrophage differentiation inversely correlating with FPR2 upregulation; miR-181b overexpression blunts LXA4- and RvD1-stimulated phagocytic activity of macrophages. Luciferase 3'-UTR reporter, miR-181b overexpression and knockdown, flow cytometric phagocytosis assay, Western blot, qPCR in human macrophages The Journal of biological chemistry High 25505240
2002 TNFα upregulates FPR2 gene expression in mouse microglial cells via the p55 TNFα receptor and p38 MAPK activation, conferring chemotactic responsiveness to Aβ42 and other FPR2 agonists, while simultaneously downregulating CXCR4 responses. Primary murine microglia and N9 cell line, TNFα stimulation, p55 receptor-specific experiments, p38 MAPK inhibition, chemotaxis assays Neurobiology of disease Medium 12270697
2014 A pepducin derived from the third intracellular loop of FPR2 activates FPR2 as a partial agonist for direct activation but as a full agonist for cross-talk-mediated reactivation via PAFR and P2Y2R; cross-talk reactivation of desensitized FPR2 is blocked by FPR2-specific inhibitors, establishing a receptor cross-talk mechanism for FPR2 reactivation. Pepducin pharmacology in human neutrophils, receptor desensitization/reactivation assays, calcium flux, FPR2-specific inhibitors PloS one Medium 25303226
2010 FPR2-mediated calcium signaling follows the same route as FPR1, requiring emptying of intracellular stores before plasma membrane channel opening; the gelsolin-derived PIP2-binding peptide PBP10 selectively inhibits FPR2-induced NADPH-oxidase activity and calcium flux. EGTA chelation experiments, PBP10 peptide inhibitor, calcium flux, NADPH-oxidase activity in human neutrophils BMC cell biology Medium 20602801
2014 RhoA/ROCK activation downstream of FPR2 negatively regulates NADPH-oxidase activity in mouse bone marrow neutrophils; FPR2 activation generates different kinetics of RhoA activation compared to FPR1, and RhoA/ROCK-mediated downregulation of FPR2-induced oxidase is dependent on cytoskeleton integrity. CT04 RhoA inhibitor, Y27632 ROCK inhibitor, cytochalasin D cytoskeleton disruption, RhoA translocation imaging, respiratory burst assay in mouse bone marrow PMNs Cellular signalling Medium 24880063
2020 FPR2 directly interacts with kinase TAK1 (demonstrated by co-immunoprecipitation) and Fpr2 deficiency reduces LPS-induced TAK1 activation, NF-κB and MAPK signaling, and oxidative stress in macrophages and in vivo lung injury models, with Nrf2 mediating part of the antioxidative effects. Co-immunoprecipitation, Fpr2 knockout mice, siRNA knockdown, Western blot for TAK1 activation, LPS-induced acute lung injury model Biomedicine & pharmacotherapy Medium 32106380
2020 ANXA1/FPR2 signaling promotes Schwann cell proliferation and migration via downstream AMPK activation; Schwann cells lacking FPR2 or AMPK show defective proliferation and migration, and ANXA1 administration accelerated nerve regeneration in a facial nerve crush model in vivo. FPR2 and AMPK siRNA/KO in Schwann cells, proliferation/migration assays, in vivo facial nerve crush model FASEB journal Medium 32856352
2019 The AnxA1/Fpr2 signaling axis directly regulates platelet function: AnxA1 suppresses thrombin-induced Akt activation, intracellular calcium release, and Rap1 expression to decrease αIIbβ3 integrin activation without altering surface expression, and promotes phosphatidylserine exposure for neutrophil phagocytosis of platelets; effects were blocked by FPR2 antagonist WRW4. Intravital microscopy, flow cytometry on human platelets, AnxA1-/- and WRW4 pharmacological blockade, in vivo cerebral I/R model Circulation High 31154815
2015 Annexin A1 secreted by skeletal muscle (palmitate-induced) acts via FPR2 to protect against insulin resistance through PKC-θ modulation; identified by quantitative proteomics of the myotube secretome and validated by FPR2 agonist treatment in L6 myotubes and high-fat diet mice. Quantitative secretome proteomics, FPR2 agonist treatment in L6 myotubes, high-fat diet mouse model, PKC-θ pathway analysis Molecular & cellular proteomics Medium 25616869
2021 FPR2/ALX activation by Ac2-26 shifts microglia/macrophage polarization toward M2 phenotype via the AMPK/mTOR pathway; WRW4 (FPR2 antagonist) abrogated these effects in vivo in cerebral I/R injury, establishing FPR2-dependent AMPK activation as the mechanistic link. tMCAO/R mouse model, WRW4 antagonist, BV2/HT22 OGD/R in vitro model, Western blot for AMPK/mTOR, flow cytometry for macrophage phenotyping Journal of neuroinflammation Medium 34022892
2021 FPR2 deletion in myeloid cells reduces macrophage chemotaxis (serum amyloid A3-mediated via FPR2) and M1 polarization by blocking their signals; bone marrow transplantation between WT and Fpr2-/- mice confirmed that myeloid Fpr2 drives adipose tissue inflammation and exacerbates diet-induced obesity/insulin resistance. Global and myeloid-specific Fpr2 knockout mice, bone marrow transplantation, HFD model, macrophage chemotaxis assays, flow cytometry Diabetes High 30862681
2023 Columbamine (COL) acts as a biased FPR2 agonist occupying part of the orthosteric binding pocket; it enhances macrophage efferocytosis by promoting LC3-associated phagocytosis (LAP); Fpr2 genetic ablation or FPR2 antagonism abolishes COL-induced LAP, anti-colitis activity, demonstrating FPR2 as a target for modulating LC3-associated efferocytosis. Transcriptome analysis, pharmacological FPR2 antagonism, Fpr2 knockout mice, colitis model, autophagy assays (LAP) EMBO molecular medicine High 37994307
2020 RvD1 signals through ALX/FPR2 on macrophages to induce a pro-revascularization transcriptional program; myeloid-specific Alx/Fpr2-deficient mice show impaired perfusion recovery and vascularization after hindlimb ischemia, with altered expression of pro-revascularization genes in skeletal muscle macrophages. RNA sequencing, myeloid-specific Alx/Fpr2-/- mice, hindlimb ischemia model, cutaneous wound model, perfusion measurement Proceedings of the National Academy of Sciences of the United States of America High 32513697
2022 E2F1-driven PRSS22 cleaves ANXA1 to generate an N-terminal peptide that activates FPR2/ERK signaling, promoting breast cancer invasion and metastasis; PRSS22-ANXA1 interaction was confirmed by protein mass spectrometry, co-IP, and western blot; co-overexpression of PRSS22 and ANXA1 enhanced migration/invasion via FPR2/ERK. Protein mass spectrometry, co-immunoprecipitation, luciferase/ChIP for E2F1-PRSS22 transcriptional regulation, in vitro invasion assays, xenograft mouse model Cell death & disease Medium 36414640
2021 FPR2 activation by WKYMVm (pro-resolving agonist) induces NADPH oxidase-dependent phosphorylation of HSP27 (Ser82), OSR1 (Ser339), and MARCKS (Ser170) via upstream kinases p38MAPK, PI3K, and PKCδ respectively; NADPH oxidase inhibition and p22phox CRISPR/Cas9 deletion prevent these phosphorylation events. NADPH oxidase inhibitors, p22phox CRISPR/Cas9 double nickase CaLu-6 cells, phospho-specific Western blot Antioxidants Medium 33477989
2022 RvD1/FPR2 signaling on alveolar macrophages attenuates HMGB1/TNF-α secretion and promotes efferocytosis of apoptotic neutrophils, while RvD1 treatment in FPR2-/- mice fails to mitigate lung IR injury, establishing FPR2 as the required receptor for RvD1-mediated resolution in lung transplantation. FPR2-/- mice, hilar-ligation IR model, orthotopic lung transplant model, in vitro alveolar macrophage assays, cytokine measurement The Journal of heart and lung transplantation High 36628837

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 The fibrinolytic receptor for urokinase activates the G protein-coupled chemotactic receptor FPRL1/LXA4R. Proceedings of the National Academy of Sciences of the United States of America 303 11818541
2002 Serum amyloid A induces IL-8 secretion through a G protein-coupled receptor, FPRL1/LXA4R. Blood 267 12393391
2013 Ligand-specific conformational change of the G-protein-coupled receptor ALX/FPR2 determines proresolving functional responses. Proceedings of the National Academy of Sciences of the United States of America 262 24108355
2021 Annexin A1 protects against cerebral ischemia-reperfusion injury by modulating microglia/macrophage polarization via FPR2/ALX-dependent AMPK-mTOR pathway. Journal of neuroinflammation 211 34022892
2010 FPR2/ALX receptor expression and internalization are critical for lipoxin A4 and annexin-derived peptide-stimulated phagocytosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 159 20570963
2013 Distinct signaling cascades elicited by different formyl peptide receptor 2 (FPR2) agonists. International journal of molecular sciences 149 23549262
2019 Novel Role for the AnxA1-Fpr2/ALX Signaling Axis as a Key Regulator of Platelet Function to Promote Resolution of Inflammation. Circulation 123 31154815
2012 Annexin A1 interaction with the FPR2/ALX receptor: identification of distinct domains and downstream associated signaling. The Journal of biological chemistry 117 22610094
1992 Mapping of genes for the human C5a receptor (C5AR), human FMLP receptor (FPR), and two FMLP receptor homologue orphan receptors (FPRH1, FPRH2) to chromosome 19. Genomics 115 1612600
2014 FPR2/ALXR agonists and the resolution of inflammation. Journal of medicinal chemistry 114 25365541
2014 Nonredundant protective properties of FPR2/ALX in polymicrobial murine sepsis. Proceedings of the National Academy of Sciences of the United States of America 106 25512512
2014 The role of the FPR2/ALX receptor in atherosclerosis development and plaque stability. Cardiovascular research 105 25341894
1999 A synthetic peptide derived from human immunodeficiency virus type 1 gp120 downregulates the expression and function of chemokine receptors CCR5 and CXCR4 in monocytes by activating the 7-transmembrane G-protein-coupled receptor FPRL1/LXA4R. Blood 103 10438703
2018 Resolvin D1 Halts Remote Neuroinflammation and Improves Functional Recovery after Focal Brain Damage Via ALX/FPR2 Receptor-Regulated MicroRNAs. Molecular neurobiology 94 29357041
1999 N-formylpeptides induce two distinct concentration optima for mouse neutrophil chemotaxis by differential interaction with two N-formylpeptide receptor (FPR) subtypes. Molecular characterization of FPR2, a second mouse neutrophil FPR. The Journal of experimental medicine 94 10477558
2005 Role of formyl peptide receptor-like 1 (FPRL1/FPR2) in mononuclear phagocyte responses in Alzheimer disease. Immunologic research 92 15888909
2000 Serum amyloid A is a chemotactic agonist at FPR2, a low-affinity N-formylpeptide receptor on mouse neutrophils. Biochemical and biophysical research communications 84 10753626
2014 Lipoxin A₄ modulates adaptive immunity by decreasing memory B-cell responses via an ALX/FPR2-dependent mechanism. European journal of immunology 79 24166736
2012 Cell surface receptor FPR2 promotes antitumor host defense by limiting M2 polarization of macrophages. Cancer research 79 23139214
2012 Leukocyte recruitment in the brain in sepsis: involvement of the annexin 1-FPR2/ALX anti-inflammatory system. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 65 22964301
2019 Fpr2 Deficiency Alleviates Diet-Induced Insulin Resistance Through Reducing Body Weight Gain and Inhibiting Inflammation Mediated by Macrophage Chemotaxis and M1 Polarization. Diabetes 61 30862681
2021 Targeting the AnxA1/Fpr2/ALX pathway regulates neutrophil function, promoting thromboinflammation resolution in sickle cell disease. Blood 60 33512489
2019 The Annexin A1/FPR2 pathway controls the inflammatory response and bacterial dissemination in experimental pneumococcal pneumonia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 59 31908042
2016 Biomarker-guided clinical development of the first-in-class anti-inflammatory FPR2/ALX agonist ACT-389949. British journal of clinical pharmacology 59 27730665
2020 Functions of resolvin D1-ALX/FPR2 receptor interaction in the hemoglobin-induced microglial inflammatory response and neuronal injury. Journal of neuroinflammation 58 32795323
2007 F2L, a peptide derived from heme-binding protein, chemoattracts mouse neutrophils by specifically activating Fpr2, the low-affinity N-formylpeptide receptor. Journal of immunology (Baltimore, Md. : 1950) 58 17237393
2020 Discovery of BMS-986235/LAR-1219: A Potent Formyl Peptide Receptor 2 (FPR2) Selective Agonist for the Prevention of Heart Failure. Journal of medicinal chemistry 57 32407089
2002 Up-regulation of FPR2, a chemotactic receptor for amyloid beta 1-42 (A beta 42), in murine microglial cells by TNF alpha. Neurobiology of disease 56 12270697
2016 Lipoxin A4 activates ALX/FPR2 receptor to regulate conjunctival goblet cell secretion. Mucosal immunology 55 27072607
2021 Recent advances in the design and development of formyl peptide receptor 2 (FPR2/ALX) agonists as pro-resolving agents with diverse therapeutic potential. European journal of medicinal chemistry 52 33486199
2013 ALX/FPR2 receptor for RvD1 is expressed and functional in salivary glands. American journal of physiology. Cell physiology 52 24259417
2011 Transcriptional regulation of the human FPR2/ALX gene: evidence of a heritable genetic variant that impairs promoter activity. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 52 22131270
2020 LXA4-FPR2 signaling regulates radiation-induced pulmonary fibrosis via crosstalk with TGF-β/Smad signaling. Cell death & disease 51 32811815
2021 Selective FPR2 Agonism Promotes a Proresolution Macrophage Phenotype and Improves Cardiac Structure-Function Post Myocardial Infarction. JACC. Basic to translational science 50 34466754
2022 Lipoxin A4 regulates M1/M2 macrophage polarization via FPR2-IRF pathway. Inflammopharmacology 44 35235107
2020 Myeloid ALX/FPR2 regulates vascularization following tissue injury. Proceedings of the National Academy of Sciences of the United States of America 44 32513697
2019 Annexin A1 attenuates neuroinflammation through FPR2/p38/COX-2 pathway after intracerebral hemorrhage in male mice. Journal of neuroscience research 44 31157469
2019 The annexin A1/FPR2 signaling axis expands alveolar macrophages, limits viral replication, and attenuates pathogenesis in the murine influenza A virus infection model. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 44 31398292
2017 FPR2 signaling without β-arrestin recruitment alters the functional repertoire of neutrophils. Biochemical pharmacology 44 28855087
2016 The G-protein coupled chemoattractant receptor FPR2 promotes malignant phenotype of human colon cancer cells. American journal of cancer research 43 27904774
2015 Proteomic analysis of the palmitate-induced myotube secretome reveals involvement of the annexin A1-formyl peptide receptor 2 (FPR2) pathway in insulin resistance. Molecular & cellular proteomics : MCP 43 25616869
2013 Treating neutrophilic inflammation in COPD by targeting ALX/FPR2 resolution pathways. Pharmacology & therapeutics 43 23880288
2017 Novel ureidopropanamide based N-formyl peptide receptor 2 (FPR2) agonists with potential application for central nervous system disorders characterized by neuroinflammation. European journal of medicinal chemistry 42 29102463
2022 Structural basis of FPR2 in recognition of Aβ42 and neuroprotection by humanin. Nature communications 41 35365641
2002 Phagocyte activation by Trp-Lys-Tyr-Met-Val-Met, acting through FPRL1/LXA4R, is not affected by lipoxin A4. Scandinavian journal of immunology 41 12410796
2018 Lipoxin A4 Attenuates the Inflammatory Response in Stem Cells of the Apical Papilla via ALX/FPR2. Scientific reports 39 29892010
2014 MicroRNA-181b regulates ALX/FPR2 receptor expression and proresolution signaling in human macrophages. The Journal of biological chemistry 38 25505240
2019 Inhibition of FPR2 impaired leukocytes recruitment and elicited non-resolving inflammation in acute heart failure. Pharmacological research 37 31216426
2013 Heterologously expressed formyl peptide receptor 2 (FPR2/ALX) does not respond to lipoxin A₄. Biochemical pharmacology 37 23643932
2022 Resolution of inflammation via RvD1/FPR2 signaling mitigates Nox2 activation and ferroptosis of macrophages in experimental abdominal aortic aneurysms. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 36 36183323
2021 Cadmium exposure induces TNF-α-mediated necroptosis via FPR2/TGF-β/NF-κB pathway in swine myocardium. Toxicology 34 33626375
2021 Therapeutic potential of the FPR2/ALX agonist AT-01-KG in the resolution of articular inflammation. Pharmacological research 32 33493655
2020 Resolvin D1 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Increasing Treg Percentages via the ALX/FPR2 Pathway. Frontiers in physiology 31 32317985
2017 FPR2: A Novel Promising Target for the Treatment of Influenza. Frontiers in microbiology 31 28928730
2014 The formylpeptide receptor 2 (Fpr2) and its endogenous ligand cathelin-related antimicrobial peptide (CRAMP) promote dendritic cell maturation. The Journal of biological chemistry 31 24808174
2022 Resolution of post-lung transplant ischemia-reperfusion injury is modulated via Resolvin D1-FPR2 and Maresin 1-LGR6 signaling. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 30 36628837
2019 Staphylococcus aureus-Derived PSMα Peptides Activate Neutrophil FPR2 but Lack the Ability to Mediate β-Arrestin Recruitment and Chemotaxis. Journal of immunology (Baltimore, Md. : 1950) 29 31694908
2021 Time-Dependent Protective and Pro-Resolving Effects of FPR2 Agonists on Lipopolysaccharide-Exposed Microglia Cells Involve Inhibition of NF-κB and MAPKs Pathways. Cells 28 34572022
2020 Suppression of Fpr2 expression protects against endotoxin-induced acute lung injury by interacting with Nrf2-regulated TAK1 activation. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 28 32106380
2023 Enhancement of efferocytosis through biased FPR2 signaling attenuates intestinal inflammation. EMBO molecular medicine 27 37994307
2023 Lipoxin-mediated signaling: ALX/FPR2 interaction and beyond. Pharmacological research 26 37925045
2020 ANXA1 directs Schwann cells proliferation and migration to accelerate nerve regeneration through the FPR2/AMPK pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26 32856352
2020 Barbadin selectively modulates FPR2-mediated neutrophil functions independent of receptor endocytosis. Biochimica et biophysica acta. Molecular cell research 26 32916203
2012 3-(1H-indol-3-yl)-2-[3-(4-nitrophenyl)ureido]propanamide enantiomers with human formyl-peptide receptor agonist activity: molecular modeling of chiral recognition by FPR2. Biochemical pharmacology 26 23219934
2021 Pro-Resolving FPR2 Agonists Regulate NADPH Oxidase-Dependent Phosphorylation of HSP27, OSR1, and MARCKS and Activation of the Respective Upstream Kinases. Antioxidants (Basel, Switzerland) 25 33477989
2020 The Lipoxin Receptor/FPR2 Agonist BML-111 Protects Mouse Skin Against Ultraviolet B Radiation. Molecules (Basel, Switzerland) 25 32604968
2022 Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease. eLife 24 35293862
2021 The N-Formyl Peptide Receptor 2 (FPR2) Agonist MR-39 Exhibits Anti-Inflammatory Activity in LPS-Stimulated Organotypic Hippocampal Cultures. Cells 24 34204273
2018 COOH-terminal SAA1 peptides fail to induce chemokines but synergize with CXCL8 and CCL3 to recruit leukocytes via FPR2. Blood 24 29371208
2014 A pepducin derived from the third intracellular loop of FPR2 is a partial agonist for direct activation of this receptor in neutrophils but a full agonist for cross-talk triggered reactivation of FPR2. PloS one 24 25303226
2025 Metabolic signaling of ceramides through the FPR2 receptor inhibits adipocyte thermogenesis. Science (New York, N.Y.) 23 40080544
2021 Annexin A1 Attenuates Neutrophil Migration and IL-6 Expression through Fpr2 in a Mouse Model of Streptococcus suis-Induced Meningitis. Infection and immunity 23 33318141
2019 FPR2 enhances colorectal cancer progression by promoting EMT process. Neoplasma 23 31288528
2016 The role of the Annexin-A1/FPR2 system in the regulation of mast cell degranulation provoked by compound 48/80 and in the inhibitory action of nedocromil. International immunopharmacology 23 26803520
2009 The FPR2-specific ligand MMK-1 activates the neutrophil NADPH-oxidase, but triggers no unique pathway for opening of plasma membrane calcium channels. Cell calcium 23 19282028
2020 Effect of RvD1/FPR2 on inflammatory response in chorioamnionitis. Journal of cellular and molecular medicine 22 33025767
2019 RvD1binding with FPR2 attenuates inflammation via Rac1/NOX2 pathway after neonatal hypoxic-ischemic injury in rats. Experimental neurology 22 31247196
2022 Behavioral, Anti-Inflammatory, and Neuroprotective Effects of a Novel FPR2 Agonist in Two Mouse Models of Autism. Pharmaceuticals (Basel, Switzerland) 21 35215274
2021 The N-Formyl Peptide Receptor 2 (FPR2) Agonist MR-39 Improves Ex Vivo and In Vivo Amyloid Beta (1-42)-Induced Neuroinflammation in Mouse Models of Alzheimer's Disease. Molecular neurobiology 21 34468933
2017 The common promoter polymorphism rs11666254 downregulates FPR2/ALX expression and increases risk of sepsis in patients with severe trauma. Critical care (London, England) 21 28679406
2015 Stimulation of cutaneous wound healing by an FPR2-specific peptide agonist WKYMVm. Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society 21 25973651
2015 A neutrophil inhibitory pepducin derived from FPR1 expected to target FPR1 signaling hijacks the closely related FPR2 instead. FEBS letters 21 26071379
2014 RhoA/ROCK downregulates FPR2-mediated NADPH oxidase activation in mouse bone marrow granulocytes. Cellular signalling 21 24880063
2009 The pyrazolone originally reported to be a formyl peptide receptor (FPR) 2/ALX-selective agonist is instead an FPR1 and FPR2/ALX dual agonist. Journal of pharmacological sciences 21 19926937
2022 Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection. Cells 20 36078125
2022 E2F1-initiated transcription of PRSS22 promotes breast cancer metastasis by cleaving ANXA1 and activating FPR2/ERK signaling pathway. Cell death & disease 20 36414640
2021 Lipoxin A4 activates ALX/FPR2 to attenuate inflammation in Aspergillus fumigatus keratitis. International immunopharmacology 20 34162149
2019 Functional and signaling characterization of the neutrophil FPR2 selective agonist Act-389949. Biochemical pharmacology 20 31085160
2014 Identification of a novel recycling sequence in the C-tail of FPR2/ALX receptor: association with cell protection from apoptosis. The Journal of biological chemistry 20 25326384
2014 FPR2/ALX activation reverses LPS-induced vascular hyporeactivity in aorta and increases survival in a pneumosepsis model. European journal of pharmacology 20 25478948
2023 FPR2 Shapes an Immune-Excluded Pancreatic Tumor Microenvironment and Drives T-cell Exhaustion in a Sex-Dependent Manner. Cancer research 19 36919330
2018 fMLP-dependent activation of Akt and ERK1/2 through ROS/Rho A pathways is mediated through restricted activation of the FPRL1 (FPR2) receptor. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 19 29922854
2015 Non-peptide ligand binding to the formyl peptide receptor FPR2--A comparison to peptide ligand binding modes. Bioorganic & medicinal chemistry 19 25882522
2022 Annexin A1 (Ac2-26)-dependent Fpr2 receptor alleviates sepsis-induced acute kidney injury by inhibiting inflammation and apoptosis in vivo and in vitro. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 18 36544058
2021 Crosstalk Between RPE Cells and Choroidal Endothelial Cells via the ANXA1/FPR2/SHP2/NLRP3 Inflammasome/Pyroptosis Axis Promotes Choroidal Neovascularization. Inflammation 18 34595678
2018 The G-Protein-Coupled Receptor ALX/Fpr2 Regulates Adaptive Immune Responses in Mouse Submandibular Glands. The American journal of pathology 18 29684359
2011 Anti-inflammatory drugs, eicosanoids and the annexin A1/FPR2 anti-inflammatory system. Prostaglandins & other lipid mediators 18 22123264
2023 Developmental and homeostatic signaling transmitted by the G-protein coupled receptor FPR2. International immunopharmacology 17 37003185
2016 A pepducin designed to modulate P2Y2R function interacts with FPR2 in human neutrophils and transfers ATP to an NADPH-oxidase-activating ligand through a receptor cross-talk mechanism. Biochimica et biophysica acta 17 26996596
2010 The FPR2-induced rise in cytosolic calcium in human neutrophils relies on an emptying of intracellular calcium stores and is inhibited by a gelsolin-derived PIP2-binding peptide. BMC cell biology 17 20602801