Affinage

FPR1

N-formyl peptide receptor 1 · UniProt P21462

Length
350 aa
Mass
38.4 kDa
Annotated
2026-04-28
100 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

FPR1 is a Gi-coupled seven-transmembrane receptor that senses N-formyl peptides from bacteria and mitochondria as well as the endogenous ligand annexin A1, functioning as a master chemotactic receptor that directs phagocyte recruitment to sites of infection, tissue damage, and sterile inflammation. Ligand binding activates pertussis toxin-sensitive Gi2 signaling through Ras/Raf/ERK and p38 MAPK cascades, PLC-mediated calcium mobilization, and Rac1/Rac2-dependent actin remodeling that together drive chemotaxis, NADPH oxidase-dependent superoxide production, and degranulation (PMID:8040337, PMID:9062356, PMID:17954607). Beyond innate immunity, FPR1 on dendritic cells is required for immunogenic cell death signaling during anthracycline chemotherapy via annexin A1 recognition, and FPR1 serves as the entry receptor exploited by the Yersinia pestis type III secretion needle-cap protein LcrV, with Fpr1-deficient mice showing increased resistance to plague (PMID:33046534, PMID:31534221). FPR1 is also expressed in non-immune contexts including glioblastoma and neuroblastoma cells, where it transactivates EGFR to promote tumor growth and angiogenesis, and in the enteric nervous system, where it transduces commensal bacterial signals to regulate gastrointestinal motility (PMID:15928303, PMID:30930024).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1990 Medium

    The first signaling step downstream of FPR1 was placed at a pertussis toxin-sensitive G protein coupling to both PKC translocation and superoxide generation, establishing that FPR1 signals through Gi-family proteins in neutrophils.

    Evidence Pertussis toxin pretreatment of human neutrophils with subcellular PKC fractionation and superoxide assay

    PMID:2152941

    Open questions at the time
    • Gi subtype not identified
    • no direct receptor–G protein biochemistry
  2. 1994 High

    The downstream MAPK cascade was delineated: FPR1 activates Ras→Raf-1→MEK-1→ERK through Gi2, independent of PKC, establishing a canonical mitogenic signaling arm for a chemoattractant receptor.

    Evidence Immunoprecipitation kinase assays, GTP-Ras pull-down, pertussis toxin epistasis in human neutrophils

    PMID:8040337

    Open questions at the time
    • how Gi2 βγ subunits activate Ras was unresolved
    • p38 MAPK arm not yet tested
  3. 1994 High

    Chimeric receptor studies showed the FPR1 N-terminal extracellular domain is dispensable for ligand binding and membrane trafficking, redirecting attention to transmembrane and extracellular loop determinants of formyl-peptide recognition.

    Evidence C5aR/FPR and FPRH/FPR chimeric receptor transfection with radioligand binding and immunofluorescence

    PMID:8106386

    Open questions at the time
    • specific ligand-contact residues in TM domains not mapped experimentally
  4. 1997 High

    A parallel p38 MAPK pathway (via MKK3) was resolved as essential for FPR1-dependent superoxide, adhesion, and chemotaxis, while JNK was excluded, completing the bifurcation of FPR1 into ERK and p38 effector arms.

    Evidence Kinase assays, immunoprecipitation, and p38 inhibitor SK&F 86002 in human neutrophils

    PMID:9062356

    Open questions at the time
    • how p38 specifically controls NADPH oxidase vs. adhesion was unclear
  5. 1999 High

    Knockout mouse studies proved FPR1 is the high-affinity fMLF receptor mediating low-concentration chemotactic responses, resolving pharmacological ambiguity about receptor identity in mouse neutrophils.

    Evidence Fpr1-knockout mouse neutrophils, two-optimum chemotaxis assay, HEK293 transfection

    PMID:10477558

    Open questions at the time
    • mouse Fpr gene family complexity left ligand selectivity of Fpr-rs2 incompletely defined
  6. 2000 High

    Annexin A1 was identified as an endogenous FPR1 ligand that at low concentrations desensitizes neutrophils and inhibits transendothelial migration, establishing FPR1 as a receptor with dual pro- and anti-inflammatory signaling capacity depending on ligand concentration.

    Evidence Radioligand competition, Ca²⁺ flux, MAP kinase, and transendothelial migration assays in primary human neutrophils

    PMID:10882119

    Open questions at the time
    • precise structural determinants of bimodal signaling unresolved
    • in vivo relevance of annexin A1–FPR1 axis not yet tested
  7. 2003 High

    In vivo validation using Fpr1-knockout mice in an ischemia-reperfusion model showed annexin A1 peptide Ac2-26 acts through both FPR1 and FPR2/ALX to inhibit leukocyte trafficking, quantifying ~50% of anti-inflammatory activity as FPR1-dependent.

    Evidence Intravital microscopy of mesenteric microcirculation in Fpr1-KO mice with pharmacological antagonists

    PMID:12560218

    Open questions at the time
    • relative contribution of FPR1 vs FPR2 varies by tissue and model
  8. 2005 High

    Mitochondrial N-formyl peptides were shown to be potent FPR1 agonists comparable to bacterial peptides, establishing that FPR1 senses host-derived danger signals from mitochondrial damage, while bacterial formyl peptides showed 100-fold FPR1 selectivity over FPRL1.

    Evidence Ca²⁺ mobilization and chemotaxis in HL-60 lines stably expressing FPR1, FPRL1, or FPRL2

    PMID:16025565

    Open questions at the time
    • in vivo significance of mitochondrial DAMPs acting through FPR1 not yet demonstrated
  9. 2005 High

    FPR1 expression was discovered on glioblastoma cells where it drives tumor motility, proliferation, and VEGF production, extending FPR1 biology beyond innate immunity to cancer.

    Evidence siRNA knockdown with chemotaxis, BrdU, VEGF ELISA, and nude mouse xenograft

    PMID:15928303

    Open questions at the time
    • identity of endogenous glioma-derived FPR1 agonist not fully characterized
  10. 2007 High

    The cytoskeletal effectors downstream of FPR1 were dissected: Rac2 controls ARP2/3-dependent nucleation (~75% of actin assembly) and cofilin-mediated severing, while Rac1 regulates barbed-end uncapping, explaining how FPR1 coordinates directional actin polymerization for chemotaxis.

    Evidence Permeabilized neutrophils from Rac1- or Rac2-knockout mice with actin free barbed end assays

    PMID:17954607

    Open questions at the time
    • upstream GEFs linking Gi to Rac1 vs Rac2 activation not identified
  11. 2010 High

    Antibody blockade definitively attributed mitochondrial DAMP-induced neutrophil activation (Ca²⁺, chemotaxis, oxidative burst) to FPR1 rather than FPRL1, confirming FPR1 as the primary mitochondrial danger receptor on neutrophils in trauma.

    Evidence Anti-FPR1 vs anti-FPRL1 blocking antibodies with Ca²⁺, chemotaxis, and ROS assays

    PMID:20539176

    Open questions at the time
    • specific mitochondrial peptide sequences driving in vivo sterile inflammation not mapped
  12. 2011 High

    FPR1 was found to direct mesenchymal stem cell fate: activation promotes osteoblastic over adipogenic differentiation via PLC/PLD-Ca²⁺-CaMKII-ERK-CREB signaling, revealing a non-immune developmental role.

    Evidence FPR1 expression profiling, siRNA, calcium mobilization, phospho-signaling, in vivo zebrafish and rabbit bone formation

    PMID:21372136

    Open questions at the time
    • physiological source of formyl peptides in bone marrow niche unknown
  13. 2014 High

    FPR1 was identified as the receptor through which annexin A1 triggers necroptosis in keratinocytes during Stevens-Johnson syndrome/toxic epidermal necrolysis, via RIP1-RIP3 complex formation.

    Evidence Mass spectrometry of PBMC secretome, antibody depletion, RIP1/RIP3 detection, mouse SJS/TEN model with necroptosis inhibitor

    PMID:25031270

    Open questions at the time
    • why keratinocytes upregulate FPR1 in SJS/TEN is mechanistically unexplained
    • whether FPR1 directly activates necroptosis machinery or signals through intermediate kinases not defined
  14. 2019 High

    FPR1 was shown to function in enteric neurons, transducing commensal bacterial signals (Lactobacillus GG) into ROS production, MAPK1 phosphorylation, and increased cholinergic neurotransmission to regulate GI motility.

    Evidence Fpr1-KO and germ-free mice, gavage, immunoblots, FISH, ex vivo muscle contraction

    PMID:30930024

    Open questions at the time
    • specific bacterial formyl peptides responsible not identified
    • mechanism of FPR1-to-ROS coupling in neurons not delineated
  15. 2019 High

    FPR1 was revealed as the host receptor exploited by Yersinia pestis LcrV for type III secretion effector delivery into immune cells; Fpr1-deficient mice resist plague and the human FPR1-R190W variant confers neutrophil resistance.

    Evidence Protein–receptor binding, Fpr1-KO mouse plague infection, human R190W variant neutrophil functional assays

    PMID:31534221

    Open questions at the time
    • structural basis of LcrV–FPR1 interaction unresolved
    • whether other pathogens exploit FPR1 similarly not tested
  16. 2020 High

    FPR1 on dendritic cells was established as essential for immunogenic cell death during anthracycline chemotherapy: dying cancer cells release annexin A1, which activates DC FPR1 to enable antitumor immunity; FPR1 loss-of-function alleles associate with worse cancer outcomes in humans.

    Evidence FPR1-KO and ANXA1-KO tumor mouse models, DC and T-cell assays, human clinical allele data

    PMID:33046534

    Open questions at the time
    • downstream signaling in DCs linking FPR1 to antigen cross-presentation not mapped
    • whether FPR1 allele effect extends beyond anthracycline regimens unknown
  17. 2020 Medium

    Biased agonism at FPR1 was demonstrated: compound RE-04-001 potently activates PLC-Ca²⁺ and ERK but minimally recruits β-arrestin, showing that FPR1 signaling outputs are dissociable and ligand-dependent.

    Evidence Ca²⁺ flux, ROS, BRET β-arrestin recruitment, chemotaxis in neutrophils and HL-60 cells

    PMID:33040403

    Open questions at the time
    • structural basis for biased signaling at FPR1 unknown
    • single compound; generalizability to other biased ligands not shown

Open questions

Synthesis pass · forward-looking unresolved questions
  • High-resolution structural data for FPR1 bound to diverse ligands (formyl peptides, annexin A1, LcrV) are needed to explain ligand selectivity, biased agonism, and the pathogen exploitation mechanism, and the signaling events downstream of FPR1 on dendritic cells that link to antigen cross-presentation remain undefined.
  • no experimental FPR1 structure in the timeline
  • GEFs coupling Gi to Rac1/Rac2 not identified
  • DC-intrinsic FPR1 signaling cascade for immunogenic cell death unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 4
Partners
ANXA1EGFRGNAI2MAPK1MAPK14RAC1RAC2

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 FPR1 is a seven-transmembrane, G protein-coupled receptor expressed mainly on phagocytic leukocytes that binds N-formyl peptides (including fMLF) as well as annexin 1 and its N-terminal fragments, mediating chemotaxis and activation of phagocytes; the receptor family shares significant sequence homology with FPR2/ALX and FPR3. Pharmacological characterization, radioligand binding, functional assays in transfected cells Pharmacological reviews High 19498085
2000 Annexin I (lipocortin I) acts as an endogenous ligand of FPR1 on human neutrophils; N-terminal peptides of annexin I bind FPR and trigger Ca2+ transients and MAP kinase signaling in a dose-dependent manner, and at lower concentrations specifically inhibit transendothelial migration and desensitize neutrophils toward chemoattractant challenge. Radioligand competition binding, Ca2+ flux assays, transendothelial migration assays, MAP kinase activation assays in primary human neutrophils Molecular cell High 10882119
1994 FMLP stimulation of FPR1 on human neutrophils activates Ras and Raf-1 kinase through a pertussis toxin-sensitive Gi2 protein, leading to MEK-1 and MAP kinase activation independently of protein kinase C, suggesting Gi2-mediated receptor signaling through the Ras/Raf/MAP kinase pathway. Immunoprecipitation kinase assays, [32P]GTP labeling of Ras, pertussis toxin inhibition, in vitro MEK phosphorylation assay The Journal of clinical investigation High 8040337
1997 FMLP acting through FPR1 on human neutrophils activates p38 MAPK via MKK3, activates ERK (p42/44 MAPK) via pertussis toxin-sensitive G protein and MEKK1/Raf, but does not activate JNKs; p38 MAPK inhibition blocks superoxide production, adhesion, and chemotaxis downstream of FPR1. Kinase activity assays, immunoprecipitation, pertussis toxin inhibition, p38 MAPK inhibitor (SK&F 86002), functional neutrophil assays The Journal of clinical investigation High 9062356
2003 In vivo, annexin 1 peptide Ac2-26 inhibits leukocyte adhesion and emigration through both FPR1 and ALXR (FPR2); in FPR1-deficient mice, Ac2-26 retains ~50% inhibitory activity blocked by the FPR antagonist Boc2, while FPR1-deficient neutrophils still express ALXR and respond to lipoxin A4 and Ac2-26 to detach adherent leukocytes. Intravital microscopy of mouse mesenteric microcirculation I/R model, FPR1-knockout mice, receptor antagonist pharmacology, RT-PCR and protein detection of ALXR Blood High 12560218
2005 Human mitochondria-derived N-formylated hexapeptides (fMMYALF, fMLKLIV, fMFADRW) are potent agonists equally active on FPR1 and FPRL1 (EC50 ~10–160 nM), whereas Listeria monocytogenes-derived bacterial peptides are 100-fold more potent on FPR1 than FPRL1; none activate FPRL2. Fura-2 calcium mobilization assays in HL-60 cell lines stably transfected with FPR1, FPRL1, or FPRL2; chemotaxis assays European journal of immunology High 16025565
2010 Mitochondrial degradation products activate human neutrophils via FPR1 (not FPRL1); anti-FPR1 antibody completely blocked mitochondrial peptide-induced intracellular Ca2+ responses, and mitochondrial peptides induced FPR1-dependent chemotaxis and oxidative burst comparable to fMLF. Cytosolic Ca2+ measurements with antibody blockade of FPR1 vs FPRL1, trans-well chemotaxis assays, oxidative burst assay with carboxycarboxy-2',7'-dichlorodihydrofluorescein diacetate The Journal of trauma High 20539176
1999 Mouse FPR2 (encoded by Fpr-rs2) is a low-affinity N-formylpeptide receptor expressed on neutrophils; fMLF induces two distinct concentration optima for chemotaxis in normal mouse neutrophils (high- and low-affinity), but only the high-concentration optimum in FPR1-knockout neutrophils, establishing FPR1 as the high-affinity fMLF receptor mediating the lower-concentration chemotaxis response. HEK293 stable transfection, Ca2+ flux, chemotaxis assays, FPR knockout mouse neutrophils The Journal of experimental medicine High 10477558
2005 FPR1 expressed by glioblastoma cell line U-87 mediates chemotaxis (increased motility), cell proliferation, and VEGF production in response to fMLF; FPR1 siRNA knockdown substantially reduced tumorigenicity in nude mice and revealed that necrotic glioblastoma cells release endogenous FPR1 agonists. RT-PCR, chemotaxis assay, siRNA knockdown, BrdU proliferation, xenograft nude mouse model, ELISA for VEGF Journal of the National Cancer Institute High 15928303
2014 Annexin A1 released by drug-stimulated PBMCs activates FPR1 on SJS/TEN keratinocytes to trigger necroptosis via RIP1-RIP3 complex formation; SJS/TEN keratinocytes specifically upregulate FPR1 expression, and inhibition of necroptosis or absence of FPR1-annexed A1 signaling prevented keratinocyte death. Mass spectrometry identification of annexin A1, antibody depletion, RIP1/RIP3 complex detection, immunostaining for FPR1, mouse SJS/TEN model with necroptosis inhibitor Science translational medicine High 25031270
2019 LcrV, the needle cap protein of Yersinia pestis type III secretion system, binds FPR1 on human immune cells to facilitate translocation of bacterial effectors; Fpr1-deficient mice show increased survival from plague infection, and the FPR1-R190W variant in humans confers resistance to Y. pestis-mediated neutrophil destruction. Protein-receptor binding studies, Fpr1-knockout mouse infection model, functional assays with FPR1-R190W variant neutrophils Nature High 31534221
2007 Downstream of the fMLF-FPR1 receptor, Rac1 mediates uncapping of existing actin free barbed ends (FBE), whereas Rac2 regulates cofilin-mediated severing and ARP2/3-mediated de novo nucleation; relative contributions are uncapping 15%, cofilin severing 10%, ARP2/3 nucleation 75%. Neutrophils from Rac1- or Rac2-deficient mice, neutrophil permeabilization model maintaining receptor signaling, actin free barbed end assay The Journal of cell biology High 17954607
2001 The endogenous opioid spinorphin acts as a specific competitive antagonist at FPR1: it induces Ca2+ flux in normal mouse neutrophils and FPR1-transfected HEK293 cells but is inactive in FPR1-knockout neutrophils and FPR2-expressing cells, and blocks fMLF-induced FPR1-selective chemotaxis without affecting FPR2-selective responses. Ca2+ flux assays, FPR1-knockout mouse neutrophils, FPR1- and FPR2-transfected HEK293 cells, chemotaxis assays Journal of immunology High 11714831
2012 FPR1 is required for effective neutrophil recruitment to the damaged lung; Fpr1-/- mice are protected from bleomycin-induced pulmonary fibrosis due to failure to recruit neutrophils, and adoptive transfer shows this defect is intrinsic to fpr1-/- neutrophils rather than the lung environment. Fpr1 knockout mice, bleomycin lung fibrosis model, adoptive transfer of wild-type neutrophils into fpr1-/- mice, cell counting JCI insight High 32102985
2019 FPR1 is required in the enteric nervous system for commensal bacteria (LGG)-mediated increases in GI motility; LGG-induced myenteric ROS production, MAPK1 phosphorylation, and increased choline acetyltransferase expression are absent in FPR1-knockout mice, and require bacterial adhesion. FPR1-knockout mice, germ-free mice, gavage experiments, immunoblots, immunostaining, fluorescence in situ hybridization, ex vivo muscle contraction assays Gastroenterology High 30930024
2020 For anthracycline-based chemotherapy to be immunogenic, dying cancer cells release annexin A1 (ANXA1) which interacts with FPR1 on dendritic cells; FPR1-deficient mice show deficient chemotherapeutic responses and earlier cancer development, and FPR1 loss-of-function alleles are associated with earlier cancer development in humans. FPR1-knockout mouse tumor models, dendritic cell and T-cell functional assays, ANXA1-knockout tumor models, human clinical data for FPR1 alleles Cancer discovery High 33046534
2012 FPR1 activation by fMLF in glioblastoma cells transactivates EGFR and promotes glioma cell chemotaxis, invasion, growth, and production of angiogenic factors; this is triggered by endogenous agonist annexin A1 released by necrotic glioma cells. RT-PCR, flow cytometry, siRNA, chemotaxis assay, EGFR transactivation assays, xenograft mouse model International immunopharmacology Medium 22863814
1994 The NH2-terminal extracellular domain of FPR1 is not critical for plasma membrane transport or high-affinity N-formyl peptide binding; replacing the NH2-terminal domain of FPR1 with that of C5aR or FPRH resulted in normal cell surface expression and ligand binding, establishing that the FPR1 N-terminus is dispensable for receptor folding/transport. C5aR/FPR chimeric receptor construction, transfection into cells, radioligand binding assays, immunofluorescence for membrane localization The Journal of biological chemistry High 8106386
1990 FMLP-induced protein kinase C translocation (membrane association) and superoxide generation in human neutrophils are both dependent on a pertussis toxin-sensitive G protein, whereas PMA-, ionomycin-, or A23187-induced PKC translocation and superoxide generation are pertussis toxin-insensitive, placing FPR1 upstream of a Gi-dependent PKC activation cascade. Pertussis toxin pretreatment, subcellular fractionation for PKC activity, superoxide generation assay Journal of leukocyte biology Medium 2152941
2011 FPR1 (not FPR2 or FPR3) is upregulated during osteoblastic differentiation of human bone marrow mesenchymal stem cells; fMLP acting through FPR1 promotes osteoblastic commitment via FPR1-PLC/PLD-Ca2+-CaMKII-ERK-CREB signaling and suppresses adipogenic commitment, with FPR1 antagonist cyclosporine H blocking these effects. qPCR, flow cytometry for FPR expression, calcium mobilization, western blot for phospho-signaling, siRNA knockdown, osteogenic/adipogenic differentiation assays, zebrafish and rabbit in vivo bone formation The Journal of biological chemistry High 21372136
2016 FPR1 expressed in neuroblastoma cells mediates calcium mobilization and activates MAPK/Erk, PI3K/Akt, and p38-MAPK signaling upon fMLP stimulation; FPR1 shRNA knockdown delayed xenograft tumor development, while FPR1 overexpression promoted tumorigenesis in nude mice. Calcium mobilization assay, phospho-specific western blots, shRNA knockdown, cDNA overexpression, nude mouse xenograft model BMC cancer High 27432059
2016 FPR1 mediates neutrophil recruitment to LPS-induced lung injury and jointly with CCR5 orchestrates neutrophil infiltration; Fpr1-/- mice or mice treated with FPR1 antagonist showed reduced neutrophil counts in all lung compartments, reduced edema, and reduced histological lung damage. Fpr1-knockout mice, LPS aerosol model, pharmacological FPR1 antagonist, lung compartment neutrophil counting Journal of innate immunity Medium 23860188
2005 The uPAR-derived SRSRY peptide stimulates cell migration and F-actin polarization via FPR1; fMLF at 100 nM inhibits SRSRY-stimulated migration, and SRSRY promotes FPR1-dependent vitronectin release and increased uPAR·αvβ5 vitronectin receptor association, with αvβ5 required for ERK1/2 phosphorylation downstream of FPR1. Chemotaxis assays with alanine-substituted SRSRY analogues, F-actin staining, competitive binding with fMLF, ERK1/2 phosphorylation, co-immunoprecipitation of uPAR and αvβ5 The Journal of biological chemistry Medium 15866865
2020 The small compound RE-04-001 specifically activates FPR1 at very low concentrations (EC50 ~1 nM for NADPH-oxidase activation) and is a biased agonist that strongly activates the PLC-PIP2-Ca2+ pathway and ERK1/2 but shows minimal β-arrestin recruitment and requires higher concentrations for chemotaxis, demonstrating functional selectivity downstream of FPR1. Ca2+ flux, ROS measurement, β-arrestin recruitment assay (BRET), chemotaxis assay, receptor-specific pharmacological antagonists in human neutrophils and HL-60 cells Journal of leukocyte biology Medium 33040403
2012 Molecular dynamics simulations of FPR1 modeled on the CXCR4 template reveal that receptor activation involves a water molecule transiently bridging a hydrogen bond between W254(6.48) and N108(3.35), and a rotamer switch of Y301(7.53) facilitates movement of water molecules toward the receptor center, with agonist fMLF contacting R201(5.38) and R205(5.42) on TM5. Homology modeling using CXCR4 as template, molecular dynamics simulations of FPR1 with agonist fMLF and antagonist tBocMLF in model membrane PloS one Low 23189124
2022 FPR1 is required for splenocyte migration into ischemic brain tissue; FPR1 antagonist cFLFLFK inhibited splenocyte and monocyte/neutrophil brain infiltration and neuroinflammatory cytokine production, and fpr1-/- mice showed reduced peripheral immune cell infiltration into brain with improved neurological outcomes after stroke. Fpr1-knockout mice, transient focal brain ischemia model, FPR1 antagonist cFLFLFK, in vitro and in vivo splenocyte migration assays, cytokine measurement, neurological scoring Theranostics Medium 35547761
2022 Exposure to diabetic-range glucose impairs FPR chemotaxis signaling in neutrophils, leading to reduced chemotaxis and delayed neutrophil trafficking in wounds of Lepr(db/db) diabetic mice; CCL3 engagement of auxiliary receptors overrides the FPR signaling requirement and restores infection control. Human neutrophil chemotaxis assays at elevated glucose, Lepr(db/db) mouse wound infection model, CCL3 supplementation rescue experiments eLife Medium 35112667
2017 FPR1 blockade by cyclosporine H (CsH) inhibits neutrophil accumulation at necrotic areas in the liver during ischemia-reperfusion injury; two-photon intravital microscopy demonstrated that FPR1 signaling regulates neutrophil chemotaxis and crawling velocity into necrotic zones while not affecting monocyte/macrophage recruitment. Two-photon laser-scanning microscopy in LysM-eGFP mice, FPR1 antagonist CsH, hepatic I/R model, serum transaminases, histology Journal of immunology Medium 28062700
2015 A pepducin derived from the third intracellular loop of FPR1 inhibits neutrophil superoxide production and granule mobilization, but acts by selectively targeting FPR2 (not FPR1 as designed); the fatty acid moiety is essential for inhibition and the compound blocks FPR2 agonist binding to neutrophil surfaces. Superoxide production assay, granule mobilization assay, receptor-specific desensitization, FPR2 agonist binding competition in human neutrophils FEBS letters Medium 26071379
2016 Exogenous CO (via CORM-2) inhibits LPS-stimulated neutrophil migration toward fMLF by internalizing FPR1 through a p38 MAPK-dependent (not GRK2-dependent) mechanism. Affymetrix gene chip array, under-agarose migration assay, western blot for FPR1 internalization and p38 MAPK/GRK2 phosphorylation, in vivo LPS sepsis mouse model Oncotarget Medium 27144520

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Structure-function studies of the adipocyte-secreted hormone Acrp30/adiponectin. Implications fpr metabolic regulation and bioactivity. The Journal of biological chemistry 872 12496257
2009 International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family. Pharmacological reviews 653 19498085
1998 Neutrophils emigrate from venules by a transendothelial cell pathway in response to FMLP. The Journal of experimental medicine 281 9500793
2000 A novel ligand of the formyl peptide receptor: annexin I regulates neutrophil extravasation by interacting with the FPR. Molecular cell 270 10882119
1997 Common and distinct intracellular signaling pathways in human neutrophils utilized by platelet activating factor and FMLP. The Journal of clinical investigation 240 9062356
2001 Amyloid (beta)42 activates a G-protein-coupled chemoattractant receptor, FPR-like-1. The Journal of neuroscience : the official journal of the Society for Neuroscience 221 11160457
2003 Leukocyte antiadhesive actions of annexin 1: ALXR- and FPR-related anti-inflammatory mechanisms. Blood 174 12560218
2005 Human mitochondria-derived N-formylated peptides are novel agonists equally active on FPR and FPRL1, while Listeria monocytogenes-derived peptides preferentially activate FPR. European journal of immunology 169 16025565
1994 FMLP activates Ras and Raf in human neutrophils. Potential role in activation of MAP kinase. The Journal of clinical investigation 154 8040337
1999 Cellular responses to FMLP challenging: a mini-review. Immunopharmacology and immunotoxicology 117 10466071
2010 Mitochondrial peptides are potent immune activators that activate human neutrophils via FPR-1. The Journal of trauma 110 20539176
2005 Formylpeptide receptor FPR and the rapid growth of malignant human gliomas. Journal of the National Cancer Institute 110 15928303
2014 An annexin A1-FPR1 interaction contributes to necroptosis of keratinocytes in severe cutaneous adverse drug reactions. Science translational medicine 106 25031270
1989 The PEP: fructose phosphotransferase system in Salmonella typhimurium: FPr combines enzyme IIIFru and pseudo-HPr activities. Molecular & general genetics : MGG 97 2546043
2007 Rac1 and Rac2 differentially regulate actin free barbed end formation downstream of the fMLP receptor. The Journal of cell biology 95 17954607
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
2009 Ficolin-1 is present in a highly mobilizable subset of human neutrophil granules and associates with the cell surface after stimulation with fMLP. Journal of leukocyte biology 92 19741154
1984 Sulfasalazine inhibition of binding of N-formyl-methionyl-leucyl-phenylalanine (FMLP) to its receptor on human neutrophils. Biochemical pharmacology 87 6142713
2020 FPR-1 is an important regulator of neutrophil recruitment and a tissue-specific driver of pulmonary fibrosis. JCI insight 82 32102985
2019 Interactions Between Commensal Bacteria and Enteric Neurons, via FPR1 Induction of ROS, Increase Gastrointestinal Motility in Mice. Gastroenterology 76 30930024
1992 Tyrosine phosphorylation and its possible role in superoxide production by human neutrophils stimulated with FMLP and IgG. Biochemical and biophysical research communications 72 1372506
1994 The NH2-terminal region of C5aR but not that of FPR is critical for both protein transport and ligand binding. The Journal of biological chemistry 65 8106386
2020 Modulation of NLRP3 Inflammasome through Formyl Peptide Receptor 1 (Fpr-1) Pathway as a New Therapeutic Target in Bronchiolitis Obliterans Syndrome. International journal of molecular sciences 64 32244997
2005 Cross-talk between fMLP and vitronectin receptors triggered by urokinase receptor-derived SRSRY peptide. The Journal of biological chemistry 63 15866865
2008 Glioblastoma stem cells produce vascular endothelial growth factor by activation of a G-protein coupled formylpeptide receptor FPR. The Journal of pathology 61 18523971
2012 G protein-coupled receptor FPR1 as a pharmacologic target in inflammation and human glioblastoma. International immunopharmacology 59 22863814
2012 Genetic ablation of the fpr1 gene confers protection from smoking-induced lung emphysema in mice. American journal of respiratory cell and molecular biology 57 22461430
2019 FPR1 is the plague receptor on host immune cells. Nature 56 31534221
2010 The G-protein-coupled formylpeptide receptor FPR confers a more invasive phenotype on human glioblastoma cells. British journal of cancer 56 20197768
2003 Evaluation of human leukocyte N-formylpeptide receptor (FPR1) SNPs in aggressive periodontitis patients. Genes and immunity 53 12595898
2016 The role of formyl peptide receptor 1 (FPR1) in neuroblastoma tumorigenesis. BMC cancer 52 27432059
2013 CCR5 and FPR1 mediate neutrophil recruitment in endotoxin-induced lung injury. Journal of innate immunity 51 23860188
2010 The hederagenin saponin SMG-1 is a natural FMLP receptor inhibitor that suppresses human neutrophil activation. Biochemical pharmacology 50 20599799
1998 Chemotaxins C5a and fMLP induce release of calprotectin (leucocyte L1 protein) from polymorphonuclear cells in vitro. Molecular pathology : MP 50 9850337
2008 Superoxide anions regulate TORC1 and its ability to bind Fpr1:rapamycin complex. Proceedings of the National Academy of Sciences of the United States of America 47 18812505
1987 Platelet-leukocyte interaction: activation of rabbit platelets by FMLP-stimulated neutrophils. British journal of pharmacology 47 3118996
2022 Overriding impaired FPR chemotaxis signaling in diabetic neutrophil stimulates infection control in murine diabetic wound. eLife 44 35112667
2017 Intravital Imaging of Neutrophil Recruitment Reveals the Efficacy of FPR1 Blockade in Hepatic Ischemia-Reperfusion Injury. Journal of immunology (Baltimore, Md. : 1950) 44 28062700
2014 Development of small molecule non-peptide formyl peptide receptor (FPR) ligands and molecular modeling of their recognition. Current medicinal chemistry 43 24350845
1986 Double stimulation with FMLP and Con A restores the activation of the respiratory burst but not of the phosphoinositide turnover in Ca2+-depleted human neutrophils. A further example of dissociation between stimulation of the NADPH oxidase and phosphoinositide turnover. Biochemical and biophysical research communications 43 3022713
2020 A TLR3 Ligand Reestablishes Chemotherapeutic Responses in the Context of FPR1 Deficiency. Cancer discovery 42 33046534
2007 Production of angiogenic factors by human glioblastoma cells following activation of the G-protein coupled formylpeptide receptor FPR. Journal of neuro-oncology 41 17611713
2012 Regulation of the formyl peptide receptor 1 (FPR1) gene in primary human macrophages. PloS one 40 23185575
1992 FMLP causes eicosanoid-dependent vasoconstriction and edema in lungs from endotoxin-primed rats. The American review of respiratory disease 39 1546853
2006 hPepT1 mediates bacterial tripeptide fMLP uptake in human monocytes. Laboratory investigation; a journal of technical methods and pathology 38 16568107
2015 Gliadin Induces Neutrophil Migration via Engagement of the Formyl Peptide Receptor, FPR1. PloS one 37 26378785
2001 Contrasting evolution of the human leukocyte N-formylpeptide receptor subtypes FPR and FPRL1R. Genes and immunity 37 11607790
2011 N-formyl-methionyl-leucyl-phenylalanine (fMLP) promotes osteoblast differentiation via the N-formyl peptide receptor 1-mediated signaling pathway in human mesenchymal stem cells from bone marrow. The Journal of biological chemistry 36 21372136
2017 Dipeptide HCH6-1 inhibits neutrophil activation and protects against acute lung injury by blocking FPR1. Free radical biology & medicine 35 28232203
2005 Neutrophil NADPH-oxidase activation by an annexin AI peptide is transduced by the formyl peptide receptor (FPR), whereas an inhibitory signal is generated independently of the FPR family receptors. Journal of leukocyte biology 34 15951351
2016 Exogenous carbon monoxide inhibits neutrophil infiltration in LPS-induced sepsis by interfering with FPR1 via p38 MAPK but not GRK2. Oncotarget 33 27144520
2006 Expression analysis of the fpr (ferredoxin-NADP+ reductase) gene in Pseudomonas putida KT2440. Biochemical and biophysical research communications 33 16360643
2020 Functional selective FPR1 signaling in favor of an activation of the neutrophil superoxide generating NOX2 complex. Journal of leukocyte biology 31 33040403
2014 The intricate role of mast cell proteases and the annexin A1-FPR1 system in abdominal wall endometriosis. Journal of molecular histology 31 25201101
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2002 Cyclosporins: structure-activity relationships for the inhibition of the human FPR1 formylpeptide receptor. Journal of medicinal chemistry 29 12361388
2018 Mitochondrial peptides cause proinflammatory responses in the alveolar epithelium via FPR-1, MAPKs, and AKT: a potential mechanism involved in acute lung injury. American journal of physiology. Lung cellular and molecular physiology 28 30188748
2015 TRPC1 regulates fMLP-stimulated migration and chemotaxis of neutrophil granulocytes. Biochimica et biophysica acta 28 25595528
2007 Phospholipase D-dependent and -independent p38MAPK activation pathways are required for superoxide production and chemotactic induction, respectively, in rat neutrophils stimulated by fMLP. European journal of pharmacology 28 17560994
2006 Pharmacophore model for bile acids recognition by the FPR receptor. Journal of computer-aided molecular design 28 16972170
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2019 Elevated FPR confers to radiochemoresistance and predicts clinical efficacy and outcome of metastatic colorectal cancer patients. Aging 24 30897064
2014 FPR1 interacts with CFH, HTRA1 and smoking in exudative age-related macular degeneration and polypoidal choroidal vasculopathy. Eye (London, England) 24 25277308
2022 Molecular Structure, Expression and Role of TAFA4 and its Receptor FPR1 in the Spinal Cord. Frontiers in cell and developmental biology 23 35712659
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2009 Discovery of selective probes and antagonists for G-protein-coupled receptors FPR/FPRL1 and GPR30. Current topics in medicinal chemistry 23 19807662
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2022 Critical role of FPR1 in splenocyte migration into brain to worsen inflammation and ischemic brain injury in mice. Theranostics 22 35547761
2019 Estradiol inhibits fMLP-induced neutrophil migration and superoxide production by upregulating MKP-2 and dephosphorylating ERK. International immunopharmacology 22 31401382
2018 Involvement of the annexin A1-Fpr anti-inflammatory system in the ocular allergy. European journal of pharmacology 22 30419240
2021 Formyl Peptide Receptor (FPR)1 Modulation by Resveratrol in an LPS-Induced Neuroinflammatory Animal Model. Nutrients 21 33922475
2015 A neutrophil inhibitory pepducin derived from FPR1 expected to target FPR1 signaling hijacks the closely related FPR2 instead. FEBS letters 21 26071379
2014 MLK3 regulates fMLP-stimulated neutrophil motility. Molecular immunology 21 24389043
2008 Regulation of the leucocyte chemoattractant receptor FPR in glioblastoma cells by cell differentiation. Carcinogenesis 21 19037090
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2012 Neutrophil infiltration of the colon is independent of the FPR1 yet FPR1 deficient mice show differential susceptibilities to acute versus chronic induced colitis. Digestive diseases and sciences 18 22383080
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2007 Functional polymorphisms of the FPR1 gene and aggressive periodontitis in Japanese. Biochemical and biophysical research communications 18 17927965
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