Showing FPR2 — FPRL1 is a alias.
FPR2 (ALX/FPRL1) is a Gi-coupled G-protein-coupled receptor that orchestrates leukocyte chemotaxis, phagocytosis, and inflammatory responses by sensing a structurally diverse panel of ligands through a promiscuous orthosteric pocket (PMID:10477558, PMID:17237393, PMID:35365641). First identified as a structural homologue of the FMLP receptor FPR1 that does not recognize FMLP (PMID:1612600), it was reconstituted as a low-affinity N-formylpeptide receptor mediating high-concentration neutrophil chemotaxis (PMID:10477558). The receptor responds to host-derived agonists including serum amyloid A (PMID:12393391), the cleaved urokinase receptor fragment D2D3 (PMID:11818541), the antimicrobial peptide LL-37/CRAMP (PMID:21307335, PMID:24808174), annexin A1 (PMID:22610094, PMID:25616869), and the heme-binding protein peptide F2L (PMID:17237393), as well as pathogen-derived ligands such as HIV-1 gp120 F peptide (PMID:10438703) and staphylococcal PSMα peptides (PMID:31694908); cryo-EM structures define a polar binding cavity and hydrophobic extracellular groove governing recognition of Aβ42 and formyl humanin (PMID:35365641) and an orthosteric hydrophobic pocket accommodating long-chain ceramides that suppress adipocyte thermogenesis through Gi-cAMP signaling (PMID:40080544). Distinct ligands engage separable receptor surfaces and oligomeric states: annexin A1 binds the N-terminal region and extracellular loop II while SAA depends on extracellular loops I–II (PMID:22610094), and annexin A1 selectively activates ALX homodimers to drive p38/MK2/HSP27-IL-10 signaling whereas ALX/FPR1 heterodimers triggered by panagonists evoke JNK-dependent neutrophil apoptosis (PMID:24108355). Downstream, FPR2 signals through PLC/PKC/Ca2+, ERK/p38 MAPK, PI3K/Akt, and NADPH oxidase, with NADPH oxidase positioned upstream of HSP27, OSR1, and MARCKS phosphorylation (PMID:33477989) and required for c-Met transactivation (PMID:23583448). β-arrestin recruitment, dissociable from G-protein signaling by biased pepducin and PSMα agonists, specifically governs chemotaxis and receptor internalization rate while desensitization proceeds independently (PMID:28855087, PMID:31694908), and a C-terminal recycling sequence controls endocytic fate and anti-apoptotic survival signaling (PMID:25326384). Receptor abundance is set transcriptionally by Sp1 and promoter methylation (PMID:22131270) and post-transcriptionally by miR-181b (PMID:25250540). Through these mechanisms FPR2 mediates dendritic cell maturation and trafficking (PMID:24808174, PMID:23603910), macrophage clearance of apoptotic neutrophils (PMID:20570963), and pro-revascularization macrophage programming (PMID:32513697).
Establishing that an FPR1-homologous gene existed but did not recognize FMLP raised the question of what an orphan formyl peptide receptor homologue actually senses.
Evidence Genomic clone characterization and somatic cell hybrid chromosomal mapping
Functional reconstitution defined FPR2 as a low-affinity formyl peptide receptor and revealed it doubles as a chemotactic receptor for the HIV-1 gp120 F peptide, establishing ligand promiscuity from the outset.
Evidence Stable HEK293 transfection with calcium flux and chemotaxis assays, FPR1-knockout mouse neutrophils, and cross-desensitization studies
Identification of serum amyloid A, the cleaved uPAR fragment, and a TNF-α-inducible role in microglia expanded FPR2 into a broadly responsive inflammatory receptor with defined Gi/MAPK/NF-κB output.
Evidence HeLa overexpression with reporter and pertussis toxin assays, direct binding competition in monocytes, and microglial chemotaxis with p38 inhibitors
PMID:11818541 PMID:12270697 PMID:12393391
F2L identification with knockout validation cemented receptor-specific endogenous agonism within the FPR family.
Evidence Transfection across mouse FPR family members plus Fpr2-knockout neutrophil calcium and chemotaxis assays
Defining hierarchical C-terminal phosphorylation sites and N-terminal/TM determinants of localization, plus LL-37 as a proinflammatory agonist, began separating receptor regulation from agonist-specific output.
Evidence Site-directed mutagenesis, chimeric domain swaps, and phosphorylation/internalization assays; LL-37-driven LTB4 release with p38 and cPLA2 readouts
Chimeric mapping assigned distinct ligands to distinct receptor surfaces, and promoter analysis established Sp1/methylation control of FPR2 abundance with a functional human variant.
Evidence Chimeric FPR1/FPR2 receptors with genomic response profiling; ChIP, reporter assays, and primary neutrophil genotyping
Discovery of constitutive homo- and heterodimers with FPR1/FPR3 and of biased pepducin agonism explained how a single receptor encodes opposing pro-resolving versus pro-apoptotic outcomes, while a negative LXA4 result flagged uncertainty about lipoxin action.
Evidence BRET and Co-IP dimerization assays with primary cell signaling and knockout mice; intracellular-loop pepducins with receptor/pepducin mutagenesis and β-arrestin recruitment assays; systematic LXA4 signaling assays across orthologues
PMID:23562731 PMID:23583448 PMID:23643932 PMID:24108355 PMID:28855087
Trafficking, transcriptional, and in vivo immune studies linked receptor recycling to survival, miR-181b to receptor abundance, and CRAMP-Fpr2 signaling to dendritic cell maturation and tissue trafficking.
Evidence C-terminal recycling-sequence mutagenesis with apoptosis assays; 3'-UTR luciferase reporter with macrophage phagocytosis; Fpr2-/- and CRAMP-/- mice in dendritic cell and allergic airway models
PMID:23603910 PMID:24808174 PMID:25250540 PMID:25326384
An annexin A1-FPR2 axis in skeletal muscle extended receptor function to metabolic protection against insulin resistance.
Evidence Secretome proteomics, L6 myotube agonist treatment with PKC-θ assays, and insulin tolerance testing in high-fat-diet mice
Goblet cell studies defined a sequential phospholipase/kinase cascade for LXA4 and demonstrated heterologous desensitization between pro-resolving lipid mediators at FPR2.
Evidence Receptor immunolocalization, mucin secretion and calcium imaging, and sequential LXA4/RvD1 desensitization with pathway inhibitors
Staphylococcal PSMα peptides reinforced the biased-agonism model, with structure-activity analysis pinpointing residues required for β-arrestin recruitment and chemotaxis.
Evidence Neutrophil calcium, NADPH oxidase, ERK, β-arrestin, internalization and chemotaxis assays with PSMα2 derivative SAR
Genetic and pharmacological dissection separated β-arrestin-independent endocytosis and AP2-regulated ROS from canonical signaling, and identified a direct Fpr2-TAK1 interaction plus an RvD1-driven pro-revascularization macrophage program.
Evidence Barbadin pharmacology in β-arrestin-deficient cells with internalization/ROS assays; Co-IP of Fpr2 with TAK1 in knockout/overexpression macrophages; macrophage RNA-seq with myeloid-specific Fpr2 knockout in ischemia and wound models
PMID:32106380 PMID:32513697 PMID:32916203
Cryo-EM structures of Gi-coupled FPR2 bound to Aβ42 and formyl humanin provided the first atomic basis for ligand recognition and FPR-family selectivity, and a PRSS22 protease was shown to generate an FPR2-activating annexin A1 fragment in breast cancer.
Evidence Cryo-EM of FPR2-Gi-ligand complexes with functional validation; mass spectrometry, Co-IP and migration/invasion assays for PRSS22-ANXA1 cleavage
Discovery that FPR2 is a long-chain ceramide receptor suppressing thermogenesis via Gi-cAMP, with cryo-EM-defined orthosteric lipid binding, established a metabolic sensing function and the structural determinant convertible to FPR1/FPR3.
Evidence Three cryo-EM FPR2-Gi-ceramide structures, Gi-cAMP and thermogenesis assays in adipocytes, knockout cells, and gain-of-function mutagenesis of FPR1/FPR3
| Year | Finding | Method | Journal | Conf | PMIDs |
|---|---|---|---|---|---|
| 1992 | FPR2 (FPRH2) was identified as a structural homologue of the FMLP receptor (FPR1) that does not recognize FMLP as a ligand, and was mapped to chromosome 19 along with FPR1 and the C5a receptor. | Somatic cell hybrid panel mapping; Southern blot analysis; genomic clone characterization | Genomics | Medium | 1612600 |
| 1999 | Mouse Fpr2 (Fpr-rs2) functions as a low-affinity N-formylpeptide receptor in neutrophils; transfected HEK293 cells expressing Fpr2 responded to fMLF with calcium flux and chemotaxis at EC50 ~5 µM (~100-fold higher than FPR1). Neutrophils from FPR1-knockout mice retained only the high-concentration chemotaxis optimum, consistent with Fpr2 mediating the low-affinity/high-concentration response. | Stable transfection of HEK293 cells; calcium flux assay; chemotaxis assay; FPR knockout mouse neutrophils | The Journal of experimental medicine | High | 10477558 |
| 1999 | The HIV-1 gp120-derived F peptide (residues 414–434) uses FPRL1/FPR2 as a functional receptor to induce chemotaxis and calcium mobilization in monocytes and neutrophils; activation of FPRL1 by F peptide led to PKC-dependent downregulation of CCR5 and CXCR4 surface expression. | Transfection of receptor cDNAs; calcium mobilization assay; cross-desensitization experiments; flow cytometry; PKC inhibitor studies | Blood | High | 10438703 |
| 2002 | A soluble cleaved form of urokinase receptor (uPAR), D2D3(88-274), directly binds FPRL1/FPR2 and induces chemotaxis through this receptor. D2D3(88-274) competed for receptor binding with the synthetic agonist MMK-1 and a stable LXA4 analog. FPRL1/FPR2 is sufficient for D2D3-induced migration, whereas uPAR is required for uPA-induced chemotaxis. Receptor desensitization abolished downstream Hck tyrosine kinase activation. | Direct binding competition assay; antibody inhibition; receptor desensitization; chemotaxis assay in THP-1 cells and human monocytes; kinase phosphorylation assay | 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 in neutrophils via NF-κB, ERK1/2 and p38 MAPK. Pertussis toxin blocked IL-8 secretion; overexpression of FPRL1 in HeLa cells enhanced SAA-induced NF-κB and IL-8 reporter activity; anti-FPRL1 N-terminal antibody inhibited secretion. | Overexpression in HeLa cells; luciferase reporter assay; pertussis toxin block; calcium mobilization; MAP kinase activation assays; antibody inhibition | Blood | High | 12393391 |
| 2002 | TNF-α upregulates FPR2 expression in mouse microglial cells via the p55 TNF-α receptor and p38 MAP kinase, converting resting microglia (low FPR2, unresponsive) into cells that chemotax toward Aβ42 and other FPR2-specific agonists. | Gene expression analysis; chemotaxis assay; calcium mobilization; p38 inhibitor studies; p55 receptor-deficient cells | Neurobiology of disease | Medium | 12270697 |
| 2007 | F2L (acetylated N-terminal peptide of heme-binding protein) is a specific functional ligand for mouse Fpr2, activating calcium flux and chemotaxis with EC50 ~400–500 nM in Fpr2-transfected cells and in wild-type mouse neutrophils; Fpr2-knockout neutrophils failed to respond to F2L. | Transfection of mouse FPR family members; calcium flux assay; cAMP inhibition assay; chemotaxis assay; Fpr2-knockout mouse neutrophils | Journal of immunology | High | 17237393 |
| 2010 | PKC-dependent internalization of FPR2/ALX is required for LXA4- and Ac2-26-stimulated phagocytosis of apoptotic neutrophils by macrophages. Bone marrow macrophages from Fpr2-knockout mice failed to increase phagocytosis in response to LXA4 or Ac2-26, demonstrating a nonredundant role for this receptor. | HA-tagged receptor transfection; immunofluorescent confocal microscopy; immunogold cryo-section labeling; ELISA; bone marrow macrophages from Fpr2-/- mice; phagocytosis assay | FASEB journal | High | 20570963 |
| 2011 | FPR2/ALX undergoes agonist-dependent hierarchical phosphorylation at Ser329, Thr332, and Thr335, which is essential for receptor desensitization. Unlike FPR3, FPR2/ALX is distributed evenly at the plasma membrane in unstimulated cells. Domain-swap experiments showed the N-terminal/first TM domain governs cell surface versus intracellular localization. | Site-directed mutagenesis; chimeric receptor domain swaps; phosphorylation assays; receptor antibody uptake/internalization assays | The Journal of biological chemistry | High | 21543323 |
| 2011 | The antimicrobial peptide LL-37 signals through FPR2/ALX to promote LTB4 production from neutrophils via p38 MAP kinase and cPLA2 phosphorylation, establishing a proinflammatory LL-37/LTB4 circuit. LXA4, a known FPR2/ALX ligand, was unable to stimulate LTB4 release at tested concentrations. | Calcium mobilization assay; LTB4 release measurement; p38 and cPLA2 phosphorylation assays; pharmacological inhibitors; FPR2-transfected cell lines | FASEB journal | Medium | 21307335 |
| 2012 | AnxA1 interacts with FPR2/ALX through its N-terminal region and extracellular loop II. Chimeric FPR1/FPR2 clones identified these domains as required for AnxA1-mediated signaling; genomic responses showed domain-specific effects (N-terminal for JAG1 and JAM3 induction; dispensable for SGPP2 modulation). SAA responses depended on extracellular loops I and II; small molecule compound 43 acted via extracellular loop I with signaling through TM region II. | Chimeric receptor stably transfected in HEK293 cells; genomic response profiling; desensitization experiments | The Journal of biological chemistry | High | 22610094 |
| 2012 | The Sp1 transcription factor binds the core FPR2/ALX promoter and is required for maximal promoter activity. DNA methylation suppresses promoter activity. LXA4 enhances FPR2/ALX promoter activity and mRNA expression. A heritable A/G single nucleotide mutation in the core promoter reduces promoter activity 35–90% and reduces FPR2/ALX mRNA and protein in neutrophils from carriers. | Chromatin immunoprecipitation; site-directed mutagenesis; Sp1 overexpression; luciferase reporter assay; DNA methylation analysis; quantitative PCR and Western blot in primary neutrophils | FASEB journal | High | 22131270 |
| 2013 | FPR2/ALX (ALX) exists as constitutive homo- and heterodimers with FPR1 or FPR3. AnxA1, but not SAA, selectively activates ALX homodimers, generating a p38/MK2/HSP27 signaling signature leading to IL-10 production. ALX/FPR1 heterodimerization activated by panagonist Ac2-26 triggers a JNK-mediated pro-apoptotic pathway in neutrophils. | Coimmunoprecipitation; bioluminescence resonance energy transfer (BRET) in transfected HEK293 cells; signaling pathway analysis in primary monocytes and neutrophils; knockout mouse in vivo validation | Proceedings of the National Academy of Sciences of the United States of America | High | 24108355 |
| 2013 | FPR2 pepducin F2Pal10 (derived from the third intracellular loop) is a biased FPR2 agonist that activates PLC-PIP2-Ca2+ signaling and NADPH oxidase but does NOT recruit β-arrestin. Lack of β-arrestin recruitment was associated with reduced receptor internalization rate and impaired neutrophil chemotaxis, while receptor desensitization occurred independently of β-arrestin. | Neutrophil functional assays; calcium flux; NADPH oxidase activation; β-arrestin recruitment assay; receptor internalization assay; chemotaxis assay; cytoskeleton disruption experiments | Biochemical pharmacology | High | 28855087 |
| 2013 | Pepducins with the sequence of the third intracellular loop of FPR2 (F2Pal16, F2Pal10) activate FPR2 via an allosteric inside-in mechanism. Replacing FPR2-specific K231 with FPR1-specific Q231 abolished pepducin activity. FPR2 and FPR1 differ fundamentally in sensitivity to third intracellular loop pepducins, and the same downstream signaling pathways are activated whether initiation is outside-in or inside-in. | Neutrophil activation assays (superoxide, calcium); transfected cell lines; FPR2 antagonist competition; amino acid substitution mutagenesis of pepducin and receptor | Biochimica et biophysica acta | High | 23562731 |
| 2013 | WKYMVm (FPR2 agonist) induces transphosphorylation of c-Met (at Y1313/Y1349/Y1356) and activates STAT3, PLC-γ1/PKCα, and PI3K/Akt pathways in prostate epithelial cells; NADPH oxidase-dependent superoxide generation is critical for c-Met transactivation, as NADPH oxidase blockade prevents c-Met phosphorylation and downstream signaling. | Western blot phosphorylation assays; NADPH oxidase inhibitor studies; FPR2 agonist/antagonist pharmacology in PNT1A cells | FEBS letters | Medium | 23583448 |
| 2013 | Heterologously expressed human and murine FPR2/ALX do NOT respond to lipoxin A4 (LXA4) in calcium flux, ERK phosphorylation, cAMP reduction, or β-arrestin translocation assays, whereas the peptide agonist WKYMVM activates the same cells, raising questions about the molecular mechanism of LXA4 action. | Heterologous expression in cell lines; calcium flux; ERK phosphorylation; cAMP assay; β-arrestin translocation assay; multiple LXA4 sources and analogs tested | Biochemical pharmacology | Medium | 23643932 |
| 2014 | FPR2/ALX agonist-stimulated receptor undergoes β-arrestin-mediated endocytosis followed by rapid recycling to the plasma membrane via a C-terminal recycling sequence. Deletion of this recycling sequence alters endocytic fate and evokes pro-apoptotic effects upon agonist activation, linking receptor recycling to cell survival. | Receptor trafficking assays; β-arrestin recruitment assays; C-terminal truncation/recycling sequence mutagenesis; apoptosis assays in transfected cells | The Journal of biological chemistry | High | 25326384 |
| 2014 | Mouse Fpr2 is required for normal DC maturation: Fpr2-/- DCs failed to upregulate maturation markers, produce IL-12, chemotax toward CCL21, or stimulate allogeneic T-cell proliferation in response to LPS. This maturation defect depends on autocrine CRAMP (cathelicidin) signaling through Fpr2, as neutralization of either Fpr2 or CRAMP inhibited maturation. | Bone marrow DC culture from Fpr2-/- and CRAMP-/- mice; flow cytometry; ELISA; T-cell proliferation assay; neutralizing antibodies; in vivo antigen immunization | The Journal of biological chemistry | High | 24808174 |
| 2014 | In allergic airway inflammation, CCR2 mediates monocyte-derived DC recruitment to the perivascular region while Fpr2 is required for further migration into bronchiolar areas. The endogenous Fpr2 ligand CRAMP is present in bronchoalveolar lavage during inflammation, and CRAMP-/- mice phenocopy Fpr2-/- mice in reduced peribronchiolar DC trafficking. | Allergic airway inflammation mouse model; intravital imaging; flow cytometry; CRAMP-/- and Fpr2-/- mice; lavage fluid ligand analysis | The Journal of biological chemistry | High | 23603910 |
| 2014 | miR-181b directly binds the 3'-UTR of ALX/FPR2 mRNA (confirmed by luciferase reporter) and downregulates FPR2 protein; miR-181b overexpression reduces FPR2 protein ~25% and blunts LXA4- and RvD1-stimulated phagocytosis in macrophages. miR-181b levels decrease during monocyte-to-macrophage differentiation, inversely correlating with FPR2 upregulation. | Luciferase reporter assay with 3'-UTR; miR-181b overexpression and knockdown; Western blot; phagocytosis assay in human macrophages | The Journal of biological chemistry | High | 25250540 |
| 2015 | Annexin A1 secreted by skeletal myotubes activates FPR2 to protect against palmitate-induced insulin resistance; annexin A1 levels decrease with palmitate treatment. FPR2 agonist treatment improved systemic insulin sensitivity in high-fat diet mice, and the protective effect involved PKC-θ modulation. | Quantitative proteomics of myotube secretome; annexin A1/FPR2 agonist treatment of L6 myotubes; PKC-θ phosphorylation assay; in vivo insulin tolerance test in HFD mice | Molecular & cellular proteomics | Medium | 25616869 |
| 2016 | LXA4 activates ALX/FPR2 in conjunctival goblet cells to increase mucin secretion and intracellular Ca2+ via sequential activation of phospholipases C, D, and A2, PKC, ERK1/2, and CaM kinase. ALX/FPR2 inhibitors blocked these responses. Sequential application of LXA4 then RvD1 (or vice versa) demonstrated heterologous desensitization between the two agonists at the same receptor. | ALX/FPR2 immunolocalization; mucin secretion assay; calcium imaging; pharmacological inhibitors of ALX/FPR2 and downstream kinases; sequential agonist desensitization experiments | Mucosal immunology | Medium | 27072607 |
| 2019 | Staphylococcal PSMα peptides activate neutrophil FPR2 to increase intracellular Ca2+, ERK1/2 phosphorylation, NADPH oxidase activity, and receptor internalization, but CANNOT recruit β-arrestin or induce neutrophil chemotaxis. Structure-activity analysis with PSMα2 derivatives identified the first 3 residues linked to N-fMet and the C-terminus as critical for β-arrestin recruitment. | Neutrophil calcium flux; NADPH oxidase assay; β-arrestin recruitment assay; ERK phosphorylation; chemotaxis assay; internalization assay; PSMα2 derivative SAR analysis | Journal of immunology | High | 31694908 |
| 2020 | β-Arrestin-independent FPR2 endocytosis occurs in β-arrestin-deficient cells (albeit at reduced levels), demonstrated using Barbadin (AP2/β-arrestin interaction blocker) which inhibited AP2/β-arrestin interaction but did NOT inhibit FPR2 endocytosis. Barbadin selectively potentiated FPR2-mediated ROS production independently of β-arrestin recruitment and receptor endocytosis, suggesting AP2 regulates FPR2-mediated ROS release. | Barbadin pharmacology; β-arrestin-deficient cells; FPR2 internalization assay; NADPH oxidase ROS assay; chemotaxis assay; AP2/β-arrestin interaction assay | Biochimica et biophysica acta. Molecular cell research | High | 32916203 |
| 2020 | RvD1 binding to ALX/FPR2 on macrophages induces a transcriptional program characteristic of pro-revascularization phenotype (identified by RNA-seq). Myeloid-specific Fpr2 deficiency impairs perfusion recovery and vascularization in ischemic skeletal muscle and cutaneous wounds, associated with altered expression of pro-revascularization genes. | RNA sequencing of RvD1-treated macrophages; hindlimb ischemia model; myeloid-specific Alx/Fpr2 knockout mice; perfusion imaging; wound healing assay | Proceedings of the National Academy of Sciences of the United States of America | High | 32513697 |
| 2020 | Fpr2 directly interacts with TAK1 kinase (demonstrated by co-immunoprecipitation), and Fpr2 inhibition reduces LPS-induced TAK1 activation; this interaction promotes NF-κB and MAPK signaling and oxidative stress in macrophages. Fpr2 knockout activates Nrf2 and increases antioxidant enzymes, suggesting Nrf2 is partially downstream of Fpr2-TAK1 regulation. | Co-immunoprecipitation; Fpr2 knockout mice; Fpr2 overexpression; LPS stimulation; NF-κB and MAPK Western blots; oxidative stress assays | Biomedicine & pharmacotherapy | Medium | 32106380 |
| 2021 | FPR2 activation by WKYMVm and annexin A1 (ANXA1) leads to NADPH oxidase-dependent phosphorylation of HSP27 (Ser82), OSR1 (Ser339), and MARCKS (Ser170) via upstream kinases p38MAPK, PI3K, and PKCδ respectively; NADPH oxidase inhibition or p22phox CRISPR knockout prevents all these phosphorylation events, placing NADPH oxidase upstream of these kinase cascades. | Phosphorylation assays with site-specific antibodies; NADPH oxidase inhibitors; p22phox CRISPR/Cas9 double nickase knockout cells; agonist stimulation of CaLu-6 cells | Antioxidants | Medium | 33477989 |
| 2022 | Cryo-EM structures of FPR2 bound to Gi and either Aβ42 or N-formyl humanin (fHN) were determined. Two critical structural regions govern recognition: a polar binding cavity within the receptor helical bundle and a hydrophobic binding groove in the extracellular region. Structures of FPR2 and FPR1 with different formyl peptides provided mechanistic insights into ligand selectivity within the FPR family. | Cryo-electron microscopy structure determination; functional binding and signaling assays | Nature communications | High | 35365641 |
| 2022 | PRSS22 protease binds and cleaves ANXA1 (confirmed by Co-IP, mass spectrometry, and Western blot), generating an N-terminal peptide that activates FPR2/ERK signaling to promote breast cancer cell migration and invasion. | Protein mass spectrometry; co-immunoprecipitation; Western blot; cell migration and invasion assays; ERK phosphorylation; in vivo xenograft | Cell death & disease | Medium | 36414640 |
| 2025 | FPR2 is a membrane receptor that specifically binds long-chain ceramides (C14–C20). C16:0 ceramide binding to FPR2 inhibits thermogenesis in brown and beige adipocytes through Gi-cAMP signaling pathways. Three cryo-EM structures of FPR2-Gi complexes bound to C16:0, C18:0, and C20:0 ceramides were determined, showing hydrophobic tails embedded in the orthosteric pocket. Modification of the ceramide-binding motif in FPR1 or FPR3 converts them from inactive to active ceramide receptors. | Cryo-EM structure determination of FPR2-Gi-ceramide complexes; Gi-cAMP signaling assay; thermogenesis assay in brown/beige adipocytes; FPR2 knockout cells; mutagenesis converting FPR1/FPR3 to ceramide receptors | Science | High | 40080544 |
| 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 | 304 | 11818541 |
| 2002 | Serum amyloid A induces IL-8 secretion through a G protein-coupled receptor, FPRL1/LXA4R. | Blood | 269 | 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 | 263 | 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 | 221 | 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 | 160 | 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 | 126 | 31154815 |
| 2012 | Annexin A1 interaction with the FPR2/ALX receptor: identification of distinct domains and downstream associated signaling. | The Journal of biological chemistry | 118 | 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 | 107 | 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 | 95 | 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 | 95 | 10477558 |
| 2005 | Role of formyl peptide receptor-like 1 (FPRL1/FPR2) in mononuclear phagocyte responses in Alzheimer disease. | Immunologic research | 92 | 15888909 |
| 2014 | Lipoxin A₄ modulates adaptive immunity by decreasing memory B-cell responses via an ALX/FPR2-dependent mechanism. | European journal of immunology | 80 | 24166736 |
| 2012 | Cell surface receptor FPR2 promotes antitumor host defense by limiting M2 polarization of macrophages. | Cancer research | 79 | 23139214 |
| 2011 | Leukotriene B4/antimicrobial peptide LL-37 proinflammatory circuits are mediated by BLT1 and FPR2/ALX and are counterregulated by lipoxin A4 and resolvin E1. | FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 75 | 21307335 |
| 2019 | Fpr2 Deficiency Alleviates Diet-Induced Insulin Resistance Through Reducing Body Weight Gain and Inhibiting Inflammation Mediated by Macrophage Chemotaxis and M1 Polarization. | Diabetes | 65 | 30862681 |
| 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 |
| 2021 | Targeting the AnxA1/Fpr2/ALX pathway regulates neutrophil function, promoting thromboinflammation resolution in sickle cell disease. | Blood | 64 | 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 | 62 | 31908042 |
| 2014 | Inflammation and cancer: role of annexin A1 and FPR2/ALX in proliferation and metastasis in human laryngeal squamous cell carcinoma. | PloS one | 61 | 25490767 |
| 2020 | Functions of resolvin D1-ALX/FPR2 receptor interaction in the hemoglobin-induced microglial inflammatory response and neuronal injury. | Journal of neuroinflammation | 59 | 32795323 |
| 2016 | Biomarker-guided clinical development of the first-in-class anti-inflammatory FPR2/ALX agonist ACT-389949. | British journal of clinical pharmacology | 59 | 27730665 |
| 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 |
| 2016 | Lipoxin A4 activates ALX/FPR2 receptor to regulate conjunctival goblet cell secretion. | Mucosal immunology | 56 | 27072607 |
| 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 |
| 2005 | Functional genomics and expression analysis of the Corynebacterium glutamicum fpr2-cysIXHDNYZ gene cluster involved in assimilatory sulphate reduction. | BMC genomics | 55 | 16159395 |
| 2020 | LXA4-FPR2 signaling regulates radiation-induced pulmonary fibrosis via crosstalk with TGF-β/Smad signaling. | Cell death & disease | 53 | 32811815 |
| 2013 | ALX/FPR2 receptor for RvD1 is expressed and functional in salivary glands. | American journal of physiology. Cell physiology | 53 | 24259417 |
| 2011 | N-formyl peptide receptor 3 (FPR3) departs from the homologous FPR2/ALX receptor with regard to the major processes governing chemoattractant receptor regulation, expression at the cell surface, and phosphorylation. | The Journal of biological chemistry | 53 | 21543323 |
| 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 |
| 2021 | Selective FPR2 Agonism Promotes a Proresolution Macrophage Phenotype and Improves Cardiac Structure-Function Post Myocardial Infarction. | JACC. Basic to translational science | 52 | 34466754 |
| 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 |
| 2018 | Resolution of Inflammation Through the Lipoxin and ALX/FPR2 Receptor Pathway Protects Against Abdominal Aortic Aneurysms. | JACC. Basic to translational science | 48 | 30623131 |
| 2022 | Lipoxin A4 regulates M1/M2 macrophage polarization via FPR2-IRF pathway. | Inflammopharmacology | 47 | 35235107 |
| 2020 | Myeloid ALX/FPR2 regulates vascularization following tissue injury. | Proceedings of the National Academy of Sciences of the United States of America | 46 | 32513697 |
| 2019 | Annexin A1 attenuates neuroinflammation through FPR2/p38/COX-2 pathway after intracerebral hemorrhage in male mice. | Journal of neuroscience research | 45 | 31157469 |
| 2017 | FPR2 signaling without β-arrestin recruitment alters the functional repertoire of neutrophils. | Biochemical pharmacology | 45 | 28855087 |
| 2016 | The G-protein coupled chemoattractant receptor FPR2 promotes malignant phenotype of human colon cancer cells. | American journal of cancer research | 44 | 27904774 |
| 2022 | Structural basis of FPR2 in recognition of Aβ42 and neuroprotection by humanin. | Nature communications | 43 | 35365641 |
| 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 |
| 2002 | Phagocyte activation by Trp-Lys-Tyr-Met-Val-Met, acting through FPRL1/LXA4R, is not affected by lipoxin A4. | Scandinavian journal of immunology | 42 | 12410796 |
| 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 | 40 | 36183323 |
| 2013 | Signal relay by CC chemokine receptor 2 (CCR2) and formylpeptide receptor 2 (Fpr2) in the recruitment of monocyte-derived dendritic cells in allergic airway inflammation. | The Journal of biological chemistry | 40 | 23603910 |
| 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 |
| 2013 | The leukocyte chemotactic receptor FPR2, but not the closely related FPR1, is sensitive to cell-penetrating pepducins with amino acid sequences descending from the third intracellular receptor loop. | Biochimica et biophysica acta | 38 | 23562731 |
| 2013 | Heterologously expressed formyl peptide receptor 2 (FPR2/ALX) does not respond to lipoxin A₄. | Biochemical pharmacology | 38 | 23643932 |
| 2019 | Inhibition of FPR2 impaired leukocytes recruitment and elicited non-resolving inflammation in acute heart failure. | Pharmacological research | 37 | 31216426 |
| 2021 | Cadmium exposure induces TNF-α-mediated necroptosis via FPR2/TGF-β/NF-κB pathway in swine myocardium. | Toxicology | 35 | 33626375 |
| 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 | 34 | 36628837 |
| 2020 | Resolvin D1 Protects Against Ischemia/Reperfusion-Induced Acute Kidney Injury by Increasing Treg Percentages via the ALX/FPR2 Pathway. | Frontiers in physiology | 34 | 32317985 |
| 2013 | WKYMVm-induced cross-talk between FPR2 and HGF receptor in human prostate epithelial cell line PNT1A. | FEBS letters | 34 | 23583448 |
| 2023 | Enhancement of efferocytosis through biased FPR2 signaling attenuates intestinal inflammation. | EMBO molecular medicine | 32 | 37994307 |
| 2021 | Therapeutic potential of the FPR2/ALX agonist AT-01-KG in the resolution of articular inflammation. | Pharmacological research | 32 | 33493655 |
| 2017 | FPR2: A Novel Promising Target for the Treatment of Influenza. | Frontiers in microbiology | 32 | 28928730 |
| 2016 | ALX/FPR2 Modulates Anti-Inflammatory Responses in Mouse Submandibular Gland. | Scientific reports | 32 | 27064029 |
| 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 |
| 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) | 30 | 31694908 |
| 2012 | Characterization of the promoter and the transcriptional regulation of the lipoxin A4 receptor (FPR2/ALX) gene in human monocytes and macrophages. | Journal of immunology (Baltimore, Md. : 1950) | 30 | 22246625 |
| 2023 | Lipoxin-mediated signaling: ALX/FPR2 interaction and beyond. | Pharmacological research | 29 | 37925045 |
| 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 | 29 | 34572022 |
| 2020 | Suppression of Fpr2 expression protects against endotoxin-induced acute lung injury by interacting with Nrf2-regulated TAK1 activation. | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie | 29 | 32106380 |
| 2025 | Metabolic signaling of ceramides through the FPR2 receptor inhibits adipocyte thermogenesis. | Science (New York, N.Y.) | 27 | 40080544 |
| 2022 | Targeting the Annexin A1-FPR2/ALX pathway for host-directed therapy in dengue disease. | eLife | 26 | 35293862 |
| 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 |
| 2021 | Annexin A1 Attenuates Neutrophil Migration and IL-6 Expression through Fpr2 in a Mouse Model of Streptococcus suis-Induced Meningitis. | Infection and immunity | 25 | 33318141 |
| 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 |
| 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 | 25 | 25303226 |
| 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 |
| 2019 | RvD1binding with FPR2 attenuates inflammation via Rac1/NOX2 pathway after neonatal hypoxic-ischemic injury in rats. | Experimental neurology | 23 | 31247196 |
| 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 |
| 2022 | Behavioral, Anti-Inflammatory, and Neuroprotective Effects of a Novel FPR2 Agonist in Two Mouse Models of Autism. | Pharmaceuticals (Basel, Switzerland) | 22 | 35215274 |
| 2020 | Effect of RvD1/FPR2 on inflammatory response in chorioamnionitis. | Journal of cellular and molecular medicine | 22 | 33025767 |
| 2019 | Functional and signaling characterization of the neutrophil FPR2 selective agonist Act-389949. | Biochemical pharmacology | 22 | 31085160 |
| 2015 | A neutrophil inhibitory pepducin derived from FPR1 expected to target FPR1 signaling hijacks the closely related FPR2 instead. | FEBS letters | 22 | 26071379 |
| 2022 | Annexin A1-FPR2/ALX Signaling Axis Regulates Acute Inflammation during Chikungunya Virus Infection. | Cells | 21 | 36078125 |
| 2022 | E2F1-initiated transcription of PRSS22 promotes breast cancer metastasis by cleaving ANXA1 and activating FPR2/ERK signaling pathway. | Cell death & disease | 21 | 36414640 |
| 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 |
| 2014 | RhoA/ROCK downregulates FPR2-mediated NADPH oxidase activation in mouse bone marrow granulocytes. | Cellular signalling | 21 | 24880063 |
| 2023 | FPR2 Shapes an Immune-Excluded Pancreatic Tumor Microenvironment and Drives T-cell Exhaustion in a Sex-Dependent Manner. | Cancer research | 20 | 36919330 |
| 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.] | 20 | 36544058 |
| 2021 | Lipoxin A4 activates ALX/FPR2 to attenuate inflammation in Aspergillus fumigatus keratitis. | International immunopharmacology | 20 | 34162149 |
| 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.] | 20 | 29922854 |
| 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 | Developmental and homeostatic signaling transmitted by the G-protein coupled receptor FPR2. | International immunopharmacology | 19 | 37003185 |
| 2021 | Crosstalk Between RPE Cells and Choroidal Endothelial Cells via the ANXA1/FPR2/SHP2/NLRP3 Inflammasome/Pyroptosis Axis Promotes Choroidal Neovascularization. | Inflammation | 19 | 34595678 |
| 2015 | Non-peptide ligand binding to the formyl peptide receptor FPR2--A comparison to peptide ligand binding modes. | Bioorganic & medicinal chemistry | 19 | 25882522 |
| 2018 | The G-Protein-Coupled Receptor ALX/Fpr2 Regulates Adaptive Immune Responses in Mouse Submandibular Glands. | The American journal of pathology | 18 | 29684359 |
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