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FPR1

Family: Formylpeptide receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Biologically Significant Variants
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 350 19q13.4 FPR1 formyl peptide receptor 1 3,57
Mouse 7 364 17 A3.2 Fpr1 formyl peptide receptor 1 23
Rat 7 355 1q12 Fpr1 formyl peptide receptor 1 55
Previous and Unofficial Names
FMLP
FPR
NFPR
FMLPR
Formyl peptide
fMLP
LOC292409
Fpr1_predicted
fMet-Leu-Phe receptor
formyl peptide receptor 1
formyl peptide receptor 1 (predicted)
fMLF-R
Database Links
ChEMBL Target 13010 (Hs)
DrugBank Target 1448 (Hs)
Ensembl ENSG00000171051 (Hs), ENSMUSG00000045551 (Mm), ENSRNOG00000011174 (Rn)
Entrez Gene 2357 (Hs), 14293 (Mm), 292409 (Rn)
GeneCards FPR1 (Hs)
GenitoUrinary Development Molecular Anatomy Project Fpr1 (Mm)
HomoloGene 20466 (Hs)
Human Protein Reference Database 00646 (Hs)
InterPro P21462 (Hs), P33766 (Mm)
KEGG Gene hsa:2357 (Hs), mmu:14293 (Mm), rno:292409 (Rn)
OMIM 136537 (Hs)
PharmGKB Gene PA28244 (Hs)
PhosphoSitePlus P21462 (Hs), P33766 (Mm)
Protein Ontology (PRO) PRO:000001580 (Hs)
RefSeq Nucleotide NM_002029 (Hs), NM_013521 (Mm), NM_001106216 (Rn)
RefSeq Protein NP_002020 (Hs), NP_038549 (Mm), NP_001099686 (Rn)
TreeFam ENSG00000171051 (Hs), ENSMUSG00000045551 (Mm), ENSRNOG00000011174 (Rn)
UniProt P21462 (Hs), P33766 (Mm)
Wikipedia FPR1
Formylpeptide receptors
Search for 3D structures on the PDB
Search by keyword: Formylpeptide receptors FPR1 Search by accession number: P21462, P33766
Natural/Endogenous Ligand(s)
annexin I {Sp: Human} , annexin I {Sp: Mouse} , annexin I {Sp: Rat}
cathepsin G {Sp: Human} , cathepsin G {Sp: Mouse} , cathepsin G {Sp: Rat}
Rank order of potency (Human)
fMet-Leu-Phe > cathepsin G > annexin I  [45,79]
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
fMet-Leu-Phe-Ile-Ile-Lys-FITC Mm Full agonist 8.6 pKd 32
[3H]fMet-Leu-Phe Hs Full agonist 7.6 – 9.3 pKd 39
[125I]cathepsin G (human) Hs Full agonist 7.0 pKd 79
fMet-Ile-Val-Thr-Leu-Phe Mm Full agonist 10.7 pEC50 32
fMet-Ile-Phe-Leu Hs Full agonist 10.5 pEC50 67
fMet-Leu-Phe Hs Full agonist 10.1 – 10.2 pEC50 22,76
fMet-Met-Tyr-Ala-Leu-Phe Mm Full agonist 10.0 pEC50 32
fMet-Ile-Phe-Leu Mm Full agonist 9.5 pEC50 32
fMet-Met-Trp-Leu-Leu Hs Full agonist 9.0 pEC50 12
Met-Met-Trp-Leu-Leu Hs Full agonist 9.0 pEC50 12
WKYMVm Hs Full agonist 9.0 pEC50 42
WKYMVm Mm Full agonist 9.0 pEC50 32-33
compound 43 [PMID:23160941] Mm Full agonist 8.7 pEC50 32
fMet-Ile-Val-Ile-Leu Hs Full agonist 8.7 pEC50 66
fMet-Ile-Val-Thr-Leu-Phe Hs Full agonist 8.6 pEC50 66
T20(DP178) Hs Full agonist 8.3 pEC50 31,78
fMet-Leu-Phe-Glu Mm Full agonist 8.2 pEC50 32
fMet-Met-Tyr-Ala-Leu-Phe Hs Full agonist 8.0 pEC50 66
AG-14 Hs Full agonist 7.4 pEC50 69
annexin I {Sp: Human} Mm Full agonist 6.6 pEC50 17,63
gG-2p20 Hs Full agonist 6.2 – 6.3 pEC50 5
R-(-)-6-methyl-2,4-disubstituted pyridazin-3(2H)-one Hs Full agonist 6.0 pEC50 15
annexin I-(2-26) {Sp: Human} Hs Full agonist 5.8 – 6.1 pEC50 26,82
AG-09/1 Hs Full agonist 5.6 pEC50 38
AG-11/03 Hs Full agonist 5.6 pEC50 37
fMet-Leu-Phe Mm Full agonist 4.7 pEC50 30,77
spinorphin Mm Partial agonist 3.9 pEC50 47
View species-specific agonist tables
Agonist Comments
FPR1-mediated neutrophil functions have different requirements for agonist concentrations, from low (chemotaxis) to high (superoxide generation). Some early studies of fMet-Leu-Phe were conducted on rabbit neutrophils [9,23]. The annexin I peptides include Ac2-12, Ac2-26 and Ac9-25. These peptides bind to both FPR1 and FPR2 with similar affinities, and therefore non-selective according to IUPHAR standard [17,26,36,82]. T20/DP178, an ectodomain peptide of human immunodeficiency virus type 1 gp41, is an activator of FPR1 [78]. AG-14 (1,3-benzodioxolane-5-carboxylic acid 4`-benzyloxy-3`-methoxybenzylidene-hydrazide) represents a novel small-molecule agonist of FPR1. Selected chiral compounds are potent mixed FPR1/FPR2 agonists, among which R-(-)-forms generally exhibits higher activity than the S-(+)-enantiomers [15]. Benzimidazole derivatives include 2-(benzimidazol-2-ylthio)-N-phenylacetamide-derivatives and 2-(5-alkoxybenzimidazol-2-ylthio)-N-phenylacetamide derivatives, among which FPR1-specific agonists are AG-09/1, AG-09/2, AG-09/13, AG-09/18, AG-09/19, AG-09/21, AG-11/03, AG-11/05 and AG-11/23, while the other compounds tested in the series are mixed FPR1/FPR2 agonists or FPR2-specific agonists [37-38]. Despite acting as a calcium-mobilizing agonist at mouse Fpr1, spinorphin is a weak chemotactic agonist and effectively blocks neutrophil chemotaxis induced by fMLF at concentrations selective for mouse Fpr1 [47].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]CHIPS Hs Antagonist 7.5 pKd 29
3570-0208 [PMID:19807662] Hs Antagonist 7.0 pKi 2
cyclosporin H Hs Antagonist 6.1 – 7.1 pKi 84,87
t-Boc-FLFLF Hs Antagonist 6.0 – 6.5 pKi 84
chenodeoxycholic acid Hs Antagonist 4.0 pKi 14
deoxycholic acid Hs Antagonist 4.0 pKi 13
cyclosporin A Hs Antagonist 6.2 – 6.3 pEC50 86
BVT173187 Hs Antagonist 7.0 pIC50 11
i-Boc-Met-Leu-Phe Hs Antagonist 6.6 pIC50 18
t-Boc-FLFLF Hs Antagonist 6.6 pIC50 83
diamide 7 Hs Antagonist 6.5 pIC50 81
methionine benzimidazole 6 Hs Antagonist 6.3 pIC50 81
t-Boc-Met-Leu-Phe Hs Antagonist 6.2 pIC50 83
group E 1682-2106 [PMID:16118363] Hs Antagonist 5.3 pIC50 20
sufinpyrazone Hs Antagonist 5.0 pIC50 88
spinorphin Hs Antagonist 4.3 pIC50 47,57
Antagonist Comments
CHIPS is a 14.1 kDa protein found in more than half of the clinical strains of Staphylococcus aureus. Its N-terminal peptides of various lengths are also FPR1 antagonists but are 3 orders of magnitude less potent [29]. Boc-Met-Leu-Phe is also termed Boc1, and Boc-Phe-Leu-Phe-Leu-Phe is referred to as Boc2. The latter is an antagonist of both FPR1 and FPR2, and therefore is considered non-selective. Spinorphin is an endogenous peptide with the sequence of Leu-Val-Val-Tyr-Pro-Trp-Thr. BVT173187 (3,5-dichloro-N-(2-chloro-5-methyl-phenyl)-2-hydroxy-benzamide) fulfills the criteria for an FPR1 inhibitor selective for FPR1 over FPR2, and the potency is the same as that of cyclosporine H, but signaling through C5aR and CXCR (recognizing IL8) is also affected by BVT173187.
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Phospholipase C stimulation
Phospholipase A2 stimulation
Phospholipase D stimulation
References:  1,27,56,74
Secondary Transduction Mechanisms
Transducer Effector/Response
Calcium channel
Comments:  Increase of intracellular Ca2+ level results in opening of membrane Ca2+ channel in fMLF-stimulated cells. This response is secondary to release of Ca2+ from intracelluar stores.
References:  49,58,62,65
Tissue Distribution
Non-myeloid cells: Low levels of FPR1 transcript and protein are found in hepatocytes, platelets, endothelial cells, astrocytes, microglial cells, vascular smooth muscle cells, and fibroblasts. Using a polyclonal Ab, FPR1 expression is detected in thyroid, adrenal, motor and sensory neurons, cerebellar systems, and colon.
Species:  Human
Technique:  Immunocytochemistry
References:  4,16,41,43,53
Myeloid cells: FPR1 is primarily expressed in neutrophils, monocytes and macrophages. It is also found in eosinophils and basophils. FPR1 is not found on myeloblast cell surface but emerges gradually through stages of neutrophil maturation. Promyelocytic leukemia cell lines such as HL-60 may be differentiated to induce FPR1 expression. There is an intracellular pool of FPR1 in neutrophil granules that can be mobilized for cell surface expression.
Species:  Human
Technique:  Radioligand binding
References:  71,76,85,89
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Activation of PLD and formation of phosphatidate
Species:  Human
Tissue:  neutrophils
Response measured:  [3H] glycerol-labeled phosphatidate formation
References:  7,46,61
Activation of PLA2, resulting in the generation of arachidonic acid.
Species:  Human
Tissue:  neutrophils
Response measured:  Arachidonic acid release
References:  8,52
Agonist-induced phosphoinositide metabolism. This assay reflects FPR1-mediated PLCbeta activation, which is downstream of Gi protein activation. The activation of PLCbeta is mediated by Gbeta/gamma subunits.
Species:  Human
Tissue:  Neutrophils, leukemia cell lines expressing FPR1
Response measured:  PIP2 hydrolysis
References:  40,75,80
Agonist-induced incorporation of non-hydrolyzable GTP analogs. This assay reflects activation of the receptor-coupled Gi protien, and can be blocked by pertussis toxin treatment of the cells
Species:  Human
Tissue:  Neutrophils, FPR1-expressing cell lines
Response measured:  Increase of [35S]-GTPgS in precipitated Gi protein
References:  8,72
Ca2+ mobilization. This function is induced when FPR1 is activated by agonists. The rise of intracellular Ca2+ consists of release of Ca2+ from intracellular stores and Ca2+ influx. The function is secondary to PLCbeta activation and IP3 production, and be reproduced in various cells.
Species:  Human
Tissue:  Neutrophils and various transfected cells
Response measured:  Intracellular Ca2+ concentration
References:  49,58,62,65
Physiological Functions
Degranulation. Release of lysosozyme and beta-glucuronidase has been used in early studies of FPR1 activation. This function is reproducible with exogenously expressed FPR1.
Species:  Human
Tissue:  neutrophils
References:  6,76
Adhesion. Formylpeptides such as fMLF increase neutrophil adhesion to coated surface, believed to result from increased integrin activities.
Species:  Human
Tissue:  Myeloid cells, neutrophils
References:  10,34,54
One study indicates that fMLF has anti-nociceptive effect in mouse formalin test of nociceptive stimulation. Some of the Annexin I peptides also reduced nociceptive response.
Species:  Mouse
Tissue:  Whole animal
References:  64
Chemotaxis: Formylpeptides stimulate chemotaxis of phagocytes at low concentrations . This function is confirmed using exogenously expressed FPR1. Chemotaxis is responsible for neutrophil accumulation at sites of acute bacterial infection.
Species:  Human
Tissue:  Neutrophils from human and rabbits.
References:  22,70,76,89
Physiological Consequences of Altering Gene Expression
Silencing of the human FPR1 gene by siRNA leads to impaired chemotaxis and calcium mobilization in transfected cells, and reduced superoxide secretion in macrophages, when challenged with fMLF.
Species:  Human
Tissue:  Glioma cell line
Technique:  RNAi
References:  44
Deletion of the mouse FPR1 gene results in compromised immunity to Listeria monocytogenes infection, manifested as reduced ability of bacteria clearance and increased mortality rate. Neutrophils from the knockout mice respond poorly to fMLF.
Species:  Mouse
Tissue:  Neutrophils
Technique:  Gene targeting in embryonic stem cells
References:  24
Fpr1 (-/-) mice exhibits increased exploratory activity, reduced anxiety-like behaviour, and impaired fear memory, but normal spatial memory and learning capacity.
Species:  Mouse
Tissue:  Brain
Technique:  Gene targeting in embryonic stem cells
References:  25
Deficiency in mFpr1 and mFpr2 exacerbated the severity of the infection and increased the mortality of infected mice. The mechanism involved impaired early neutrophil recruitment to the liver with Fpr1 and Fpr2 being sole receptors for neutrophils to sense Listeria chemoattractant signals and for production of bactericidal superoxide.
Species:  Mouse
Tissue:  Neutrophils
Technique:  Gene targeting in embryonic stem cells
References:  48
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Fpr1tm1Gao Fpr1tm1Gao/Fpr1tm1Gao
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:107443  MP:0002419 abnormal innate immunity PMID: 9989980 
Fpr1tm1Gao Fpr1tm1Gao/Fpr1tm1Gao
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:107443  MP:0008720 impaired neutrophil migration PMID: 9989980 
Fpr1tm1Gao Fpr1tm1Gao/Fpr1tm1Gao
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:107443  MP:0002412 increased susceptibility to bacterial infection PMID: 9989980 
Fpr1tm1Gao Fpr1tm1Gao/Fpr1tm1Gao
involves: 129S1/Sv * 129X1/SvJ * C57BL/6		 MGI:107443  MP:0009788 increased susceptibility to bacterial infection induced morbidity/mortality PMID: 9989980 
Biologically Significant Variants
Single nucleotide polymorphisms (SNPs) have been identified in the FPR1 gene. These SNPs result in FPR variants with the following changes: I11T, V101L, R190W, N192K, A346E. Genetic analysis showed association of the N192K and R190W with the risk of having aggressive periodontitis.
Type:  Single nucleotide polymorphism
Species:  Human
References:  19,50,68
It was reported that juvenile periodontitis patients, whose neutrophils respond poorly to fMLF, carry SNPs that cause changes in F110(S) and C126W. Test of the FPR1 variants in transfected cells found defective chemotaxis and degranulation in response to fMLF, but normal cell surface expression. However, the accuracy of the original SNP study could not be confirmed.
Type:  Single nucleotide polymorphism
Species:  Human
References:  19,28,35,59,73
FPR1 C32T SNP interacts with age, is associated with higher and a 5 years increase of BP levels in healthy individuals aged less than 45 years.
Type:  Single nucleotide polymorphism
Species:  Human
References:  21
The relatively rare 348T/T genotype is associated with significantly impaired PMN chemotaxis and an increased risk for developing aggressive periodontitis in African Americans.
Type:  Single nucleotide polymorphism
Species:  Human
References:  51
The Asp192Lys polymorphism in FPR1 is significantly associated with increased susceptibility to stomach cancer among the elderly Japanese population.
Type:  Single nucleotide polymorphism
Species:  Human
References:  60

REFERENCES

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1. Amatruda, TT; Dragas-Graonic, S; Holmes, R; Perez, HD. (1995) Signal transduction by the formyl peptide receptor. Studies using chimeric receptors and site-directed mutagenesis define a novel domain for interaction with G-proteins. J. Biol. Chem., 270 (47): 28010-3. [PMID:7499283]

2. Arterburn, JB; Oprea, TI; Prossnitz, ER; Edwards, BS; Sklar, LA. (2009) Discovery of selective probes and antagonists for G-protein-coupled receptors FPR/FPRL1 and GPR30. Curr Top Med Chem, 9 (13): 1227-36. [PMID:19807662]

3. Bao, L., Gerard, N. P., Eddy, R. L. Jr., Shows, T. B. and Gerard, C. (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, 13: 437-440. [PMID:1612600]

4. Becker, EL; Forouhar, FA; Grunnet, ML; Boulay, F; Tardif, M; Bormann, BJ; Sodja, D; Ye, RD; Woska, JR; Murphy, PM. (1998) Broad immunocytochemical localization of the formylpeptide receptor in human organs, tissues, and cells. Cell Tissue Res., 292 (1): 129-35. [PMID:9506920]

5. Bellner, L; Thorén, F; Nygren, E; Liljeqvist, JA; Karlsson, A; Eriksson, K. (2005) A proinflammatory peptide from herpes simplex virus type 2 glycoprotein G affects neutrophil, monocyte, and NK cell functions. J. Immunol., 174 (4): 2235-41. [PMID:15699157]

6. Bentwood, BJ; Henson, PM. (1980) The sequential release of granule constitutents from human neutrophils. J. Immunol., 124 (2): 855-62. [PMID:6153206]

7. Billah, MM; Eckel, S; Mullmann, TJ; Egan, RW; Siegel, MI. (1989) Phosphatidylcholine hydrolysis by phospholipase D determines phosphatidate and diglyceride levels in chemotactic peptide-stimulated human neutrophils. Involvement of phosphatidate phosphohydrolase in signal transduction. J. Biol. Chem., 264 (29): 17069-77. [PMID:2793844]

8. Bokoch, GM; Gilman, AG. (1984) Inhibition of receptor-mediated release of arachidonic acid by pertussis toxin. Cell, 39 (2 Pt 1): 301-8. [PMID:6094010]

9. Boulay, F., Tardif, M., Brouchon, L. and Vignais, P. (1990) Synthesis and use of a novel N-formyl peptide derivative to isolate a human N-formyl peptide receptor cDNA. Res. Commun. Biochem. Biophys., 168: 1103-1109. [PMID:2161213]

10. Campbell, JJ; Qin, S; Bacon, KB; Mackay, CR; Butcher, EC. (1996) Biology of chemokine and classical chemoattractant receptors: differential requirements for adhesion-triggering versus chemotactic responses in lymphoid cells. J. Cell Biol., 134 (1): 255-66. [PMID:8698820]

11. Cevik-Aras, H; Kalderén, C; Jenmalm Jensen, A; Oprea, T; Dahlgren, C; Forsman, H. (2012) A non-peptide receptor inhibitor with selectivity for one of the neutrophil formyl peptide receptors, FPR 1. Biochem. Pharmacol., 83 (12): 1655-62. [PMID:22410002]

12. Chen, J; Bernstein, HS; Chen, M; Wang, L; Ishii, M; Turck, CW; Coughlin, SR. (1995) Tethered ligand library for discovery of peptide agonists. J. Biol. Chem., 270 (40): 23398-401. [PMID:7559498]

13. Chen, X; Mellon, RD; Yang, L; Dong, H; Oppenheim, JJ; Howard, OM. (2002) Regulatory effects of deoxycholic acid, a component of the anti-inflammatory traditional Chinese medicine Niuhuang, on human leukocyte response to chemoattractants. Biochem. Pharmacol., 63 (3): 533-41. [PMID:11853704]

14. Chen, X; Yang, D; Shen, W; Dong, HF; Wang, JM; Oppenheim, JJ; Howard, MZ. (2000) Characterization of chenodeoxycholic acid as an endogenous antagonist of the G-coupled formyl peptide receptors. Inflamm. Res., 49 (12): 744-55. [PMID:11211928]

15. Cilibrizzi, A; Schepetkin, IA; Bartolucci, G; Crocetti, L; Dal Piaz, V; Giovannoni, MP; Graziano, A; Kirpotina, LN; Quinn, MT; Vergelli, C. (2012) Synthesis, enantioresolution, and activity profile of chiral 6-methyl-2,4-disubstituted pyridazin-3(2H)-ones as potent N-formyl peptide receptor agonists. Bioorg. Med. Chem., 20 (12): 3781-92. [PMID:22607879]

16. Czapiga, M; Gao, JL; Kirk, A; Lekstrom-Himes, J. (2005) Human platelets exhibit chemotaxis using functional N-formyl peptide receptors. Exp. Hematol., 33 (1): 73-84. [PMID:15661400]

17. D'Acquisto, F., Paschalidis, N., Sampaio, A.L., Merghani, A., Flower, R.J. and Perretti, M. (2007) Impaired T cell activation and increased Th2 lineage commitment in Annexin-1-deficient T cells. Eur J Immunol, 37: 3131-3142. [PMID:17948261]

18. Derian, C.K., Solomon, H.F., Higgins, J.D., Beblavy, M.J., Santulli, R.J., Bridger, G.J., Pike, M.C., Kroon, D.J. and Fischman, A.J. (1996) Selective inhibition of N-formylpeptide-induced neutrophil activation by carbamate-modified peptide analogues. Biochemistry, 35: 1265-1269. [PMID:8573582]

19. Eckhardt, K; Roth, P; Günter, T; Schmidt, S; Feuerstein, TJ. (2003) Differential effects of K(ATP) channel blockers on [(3)H]-noradrenaline overflow after short- and long-term exposure to (+)-oxaprotiline or desipramine. Naunyn Schmiedebergs Arch. Pharmacol., 367 (2): 168-75. [PMID:12595958]

20. Edwards, BS; Bologa, C; Young, SM; Balakin, KV; Prossnitz, ER; Savchuck, NP; Sklar, LA; Oprea, TI. (2005) Integration of virtual screening with high-throughput flow cytometry to identify novel small molecule formylpeptide receptor antagonists. Mol. Pharmacol., 68 (5): 1301-10. [PMID:16118363]

21. El Shamieh, S; Herbeth, B; Azimi-Nezhad, M; Benachour, H; Masson, C; Visvikis-Siest, S. (2012) Human formyl peptide receptor 1 C32T SNP interacts with age and is associated with blood pressure levels. Clin. Chim. Acta, 413 (1-2): 34-8. [PMID:21144844]

22. Freer, R.J., Day, A.R., Radding, J.A., Schiffmann, E., Aswanikumar, S., Showell, H.J. and Becker, E.L. (1980) Further studies on the structural requirements for synthetic peptide chemoattractants. Biochemistry, 19: 2404-2410. [PMID:7387981]

23. Gao, J. L., Chen, H., Filie, J.D., Kozak, C.A. and Murphy, P.M. (1998) Differential expansion of the N-formylpeptide receptor gene cluster in human and mouse. Genomics, 51: 270-276. [PMID:9722950]

24. Gao, JL; Lee, EJ; Murphy, PM. (1999) Impaired antibacterial host defense in mice lacking the N-formylpeptide receptor. J. Exp. Med., 189 (4): 657-62. [PMID:9989980]

25. Gao, JL; Schneider, EH; Dimitrov, EL; Haun, F; Pham, TM; Mohammed, AH; Usdin, TB; Murphy, PM. (2011) Reduced fear memory and anxiety-like behavior in mice lacking formylpeptide receptor 1. Behav. Genet., 41 (5): 724-33. [PMID:21484271]

26. Gavins, F.N., Yona, S., Kamal, A.M., Flower, R.J. and Perretti, M. (2003) Leukocyte antiadhesive actions of annexin 1: ALXR-and FPR-related anti-inflammatory mechanisms. Blood, 101: 4140-4147. [PMID:12560218]

27. Gilman, AG. (1987) G proteins: transducers of receptor-generated signals. Annu. Rev. Biochem., 56: 615-49. [PMID:3113327]

28. Gwinn, MR; Sharma, A; De Nardin, E. (1999) Single nucleotide polymorphisms of the N-formyl peptide receptor in localized juvenile periodontitis. J. Periodontol., 70 (10): 1194-201. [PMID:10534074]

29. Haas, P.J., de Haas, C.J., Kleibeuker, W., Poppelier, M.J., van Kessel, K.P., Kruijtzer, J.A., Liskamp, R.M. and van Strijp, J.A. (2004) N-terminal residues of the chemotaxis inhibitory protein of Staphylococcus aureus are essential for blocking formylated peptide receptor but not C5a receptor. J Immunol., 173: 5704-5711. [PMID:15494522]

30. Hartt, JK; Barish, G; Murphy, PM; Gao, JL. (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. J. Exp. Med., 190 (5): 741-7. [PMID:10477558]

31. Hartt, JK; Liang, T; Sahagun-Ruiz, A; Wang, JM; Gao, JL; Murphy, PM. (2000) The HIV-1 cell entry inhibitor T-20 potently chemoattracts neutrophils by specifically activating the N-formylpeptide receptor. Biochem. Biophys. Res. Commun., 272 (3): 699-704. [PMID:10860818]

32. He, HQ; Liao, D; Wang, ZG; Wang, ZL; Zhou, HC; Wang, MW; Ye, RD. (2013) Functional characterization of three mouse formyl peptide receptors. Mol. Pharmacol., 83 (2): 389-98. [PMID:23160941]

33. He, R; Tan, L; Browning, DD; Wang, JM; Ye, RD. (2000) The synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met is a potent chemotactic agonist for mouse formyl peptide receptor. J. Immunol., 165 (8): 4598-605. [PMID:11035102]

34. Honda, S; Campbell, JJ; Andrew, DP; Engelhardt, B; Butcher, BA; Warnock, RA; Ye, RD; Butcher, EC. (1994) Ligand-induced adhesion to activated endothelium and to vascular cell adhesion molecule-1 in lymphocytes transfected with the N-formyl peptide receptor. J. Immunol., 152 (8): 4026-35. [PMID:7511663]

35. Jones, BE; Miettinen, HM; Jesaitis, AJ; Mills, JS. (2003) Mutations of F110 and C126 of the formyl peptide receptor interfere with G-protein coupling and chemotaxis. J. Periodontol., 74 (4): 475-84. [PMID:12747452]

36. Karlsson, J., Fu, H., Boulay, F., Dahlgren, C., Hellstrand, K. and Movitz, C. (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. J Leukoc Biol, 78: 762-771. [PMID:15951351]

37. Khlebnikov, AI; Schepetkin, IA; Kirpotina, LN; Brive, L; Dahlgren, C; Jutila, MA; Quinn, MT. (2012) Molecular docking of 2-(benzimidazol-2-ylthio)-N-phenylacetamide-derived small-molecule agonists of human formyl peptide receptor 1. J Mol Model, 18 (6): 2831-43. [PMID:22127612]

38. Kirpotina, LN; Khlebnikov, AI; Schepetkin, IA; Ye, RD; Rabiet, MJ; Jutila, MA; Quinn, MT. (2010) Identification of novel small-molecule agonists for human formyl peptide receptors and pharmacophore models of their recognition. Mol. Pharmacol., 77 (2): 159-70. [PMID:19903830]

39. Koo, C., Lefkowitz, R.J. and Snyderman, R. (1982) The oligopeptide chemotactic factor receptor on human polymorphonuclear leukocyte membranes exists in two affinity states. Biochem Biophys Res Commun., 106: 442-449. [PMID:6285921]

40. Krause, KH; Schlegel, W; Wollheim, CB; Andersson, T; Waldvogel, FA; Lew, PD. (1985) Chemotactic peptide activation of human neutrophils and HL-60 cells. Pertussis toxin reveals correlation between inositol trisphosphate generation, calcium ion transients, and cellular activation. J. Clin. Invest., 76 (4): 1348-54. [PMID:3877077]

41. Lacy, M; Jones, J; Whittemore, SR; Haviland, DL; Wetsel, RA; Barnum, SR. (1995) Expression of the receptors for the C5a anaphylatoxin, interleukin-8 and FMLP by human astrocytes and microglia. J. Neuroimmunol., 61 (1): 71-8. [PMID:7560015]

42. Le, Y., Gong, W., Li, B., Dunlop, N.M., Shen, W., Su, S.B., Ye, R.D. and Wang, J.M. (1999) Utilization of two seven-transmembrane, G protein-coupled receptors, formyl peptide receptor-like 1 and formyl peptide receptor, by the synthetic hexapeptide WKYMVm for human phagocyte activation. J Immunology, 163: 6777-6784. [PMID:10586077]

43. Le, Y; Hu, J; Gong, W; Shen, W; Li, B; Dunlop, NM; Halverson, DO; Blair, DG; Wang, JM. (2000) Expression of functional formyl peptide receptors by human astrocytoma cell lines. J. Neuroimmunol., 111 (1-2): 102-8. [PMID:11063827]

44. Le, Y; Iribarren, P; Zhou, Y; Gong, W; Hu, J; Zhang, X; Wang, JM. (2004) Silencing the formylpeptide receptor FPR by short-interfering RNA. Mol. Pharmacol., 66 (4): 1022-8. [PMID:15258259]

45. Le, Y; Murphy, PM; Wang, JM. (2002) Formyl-peptide receptors revisited. Trends Immunol., 23 (11): 541-8. [PMID:12401407]

46. Lehman, N; Di Fulvio, M; McCray, N; Campos, I; Tabatabaian, F; Gomez-Cambronero, J. (2006) Phagocyte cell migration is mediated by phospholipases PLD1 and PLD2. Blood, 108 (10): 3564-72. [PMID:16873675]

47. Liang, T.S., Gao, J.L., Fatemi, O., Lavigne, M., Leto, T.L. and Murphy, P.M. (2001) The endogenous opioid spinorphin blocks fMet-Leu-Phe-induced neutrophil chemotaxis by acting as a specific antagonist at the N-formylpeptide receptor subtype FPR. J Immunol, 167: 6609-6614. [PMID:11714831]

48. Liu, M; Chen, K; Yoshimura, T; Liu, Y; Gong, W; Wang, A; Gao, JL; Murphy, PM; Wang, JM. (2012) Formylpeptide receptors are critical for rapid neutrophil mobilization in host defense against Listeria monocytogenes. Sci Rep, 2: 786. [PMID:23139859]

49. Mahomed, AG; Anderson, R. (2000) Activation of human neutrophils with chemotactic peptide, opsonized zymosan and the calcium ionophore A23187, but not with a phorbol ester, is accompanied by efflux and store-operated influx of calcium. Inflammation, 24 (6): 559-69. [PMID:11128053]

50. Maney, P; Emecen, P; Mills, JS; Walters, JD. (2009) Neutrophil formylpeptide receptor single nucleotide polymorphism 348T>C in aggressive periodontitis. J. Periodontol., 80 (3): 492-8. [PMID:19254133]

51. Maney, P; Walters, JD. (2009) Formylpeptide receptor single nucleotide polymorphism 348T>C and its relationship to polymorphonuclear leukocyte chemotaxis in aggressive periodontitis. J. Periodontol., 80 (9): 1498-505. [PMID:19722801]

52. Marshall, J; Krump, E; Lindsay, T; Downey, G; Ford, DA; Zhu, P; Walker, P; Rubin, B. (2000) Involvement of cytosolic phospholipase A2 and secretory phospholipase A2 in arachidonic acid release from human neutrophils. J. Immunol., 164 (4): 2084-91. [PMID:10657662]

53. McCoy, R; Haviland, DL; Molmenti, EP; Ziambaras, T; Wetsel, RA; Perlmutter, DH. (1995) N-formylpeptide and complement C5a receptors are expressed in liver cells and mediate hepatic acute phase gene regulation. J. Exp. Med., 182 (1): 207-17. [PMID:7540650]

54. Miettinen, HM; Gripentrog, JM; Jesaitis, AJ. (1998) Chemotaxis of chinese hamster ovary cells expressing the human neutrophil formyl peptide receptor: role of signal transduction molecules and alpha5beta1 integrin. J. Cell. Sci., 111 ( Pt 14): 1921-8. [PMID:9645940]

55. Morley, AD; King, S; Roberts, B; Lever, S; Teobald, B; Fisher, A; Cook, T; Parker, B; Wenlock, M; Phillips, C; et al.. (2012) Lead optimisation of pyrazoles as novel FPR1 antagonists. Bioorg. Med. Chem. Lett., 22 (1): 532-6. [PMID:22094028]

56. Mullmann, TJ; Cheewatrakoolpong, B; Anthes, JC; Siegel, MI; Egan, RW; Billah, MM. (1993) Phospholipase C and phospholipase D are activated independently of each other in chemotactic peptide-stimulated human neutrophils. J. Leukoc. Biol., 53 (6): 630-5. [PMID:8315346]

57. Murphy, P.M., Ozcelik, T., Kenney, R.T., Tiffany, H.L., McDermott, D. and Francke, U. (1992) A structural homologue of the N-formyl peptide receptor: characterization and chromosome mapping of a peptide chemoattractant receptor family. J. Biol. Chem., 267: 7637-7643. [PMID:1373134]

58. Naccache, PH; Showell, HJ; Becker, EL; Sha'afi, RI. (1977) Transport of sodium, potassium, and calcium across rabbit polymorphonuclear leukocyte membranes. Effect of chemotactic factor. J. Cell Biol., 73 (2): 428-44. [PMID:558197]

59. Nanamori, M; He, R; Sang, H; Ye, RD. (2004) Normal cell surface expression and selective loss of functions resulting from Phe110 to Ser and Cys126 to Trp substitutions in the formyl peptide receptor. Immunol. Invest., 33 (2): 193-212. [PMID:15195697]

60. Otani, T; Ikeda, S; Lwin, H; Arai, T; Muramatsu, M; Sawabe, M. (2011) Polymorphisms of the formylpeptide receptor gene (FPR1) and susceptibility to stomach cancer in 1531 consecutive autopsy cases. Biochem. Biophys. Res. Commun., 405 (3): 356-61. [PMID:21216225]

61. Pai, JK; Siegel, MI; Egan, RW; Billah, MM. (1988) Phospholipase D catalyzes phospholipid metabolism in chemotactic peptide-stimulated HL-60 granulocytes. J. Biol. Chem., 263 (25): 12472-7. [PMID:3165977]

62. Partida-Sanchez, S., Cockayne, D.A., Monard, S., Jacobson, E.L., Oppenheimer, N., Garvy, B., Kusser, K., Goodrich, S., Howard, M., Harmsen, A., Randall, T.D. and Lund, F.E. (2001) Cyclic ADP-ribose production by CD38 regulates intracellular calcium release, extracellular calcium influx and chemotaxis in neutrophils and is required for bacterial clearance in vivo. Nat Med, 7: 1209-1216. [PMID:11689885]

63. Perretti, M; Getting, SJ; Solito, E; Murphy, PM; Gao, JL. (2001) Involvement of the receptor for formylated peptides in the in vivo anti-migratory actions of annexin 1 and its mimetics. Am. J. Pathol., 158 (6): 1969-73. [PMID:11395373]

64. Pieretti, S; Di Giannuario, A; De Felice, M; Perretti, M; Cirino, G. (2004) Stimulus-dependent specificity for annexin 1 inhibition of the inflammatory nociceptive response: the involvement of the receptor for formylated peptides. Pain, 109 (1-2): 52-63. [PMID:15082126]

65. Pozzan, T; Lew, DP; Wollheim, CB; Tsien, RY. (1983) Is cytosolic ionized calcium regulating neutrophil activation?. Science, 221 (4618): 1413-5. [PMID:6310757]

66. Rabiet, M.J., Huet, E. and Boulay, F. (2005) Human mitochondria-derived N-formylated peptides are novel agonists equally active on FPR and FPRL1, while Listeria monocytogenes-derived peptides preferentially activate FPR. Eur J Immunol, 35: 2486-2495. [PMID:16025565]

67. Rot, A., Henderson, L.E., Copeland, T.D. and Leonard, E.J. (1987) A series of six ligands for the human formyl peptide receptor: tetrapeptides with high chemotactic potency and efficacy. Proc Natl Acad Sci U S A., 84: 7967-7971. [PMID:2825171]

68. Sahagun-Ruiz, A., Colla, J.S., Juhn, J., Gao, J.L., Murphy, P.M. and McDermott, D.H. (2001) Contrasting evolution of the human leukocyte N-formylpeptide receptor subtypes FPR and FPRL1R. Genes Immun, 2: 335-342. [PMID:11607790]

69. Schepetkin, IA; Kirpotina, LN; Khlebnikov, AI; Quinn, MT. (2007) High-throughput screening for small-molecule activators of neutrophils: identification of novel N-formyl peptide receptor agonists. Mol. Pharmacol., 71 (4): 1061-74. [PMID:17229869]

70. Schiffmann, E; Corcoran, BA; Wahl, SM. (1975) N-formylmethionyl peptides as chemoattractants for leucocytes. Proc. Natl. Acad. Sci. U.S.A., 72 (3): 1059-62. [PMID:1093163]

71. Schiffmann, E; Showell, HV; Corcoran, BA; Ward, PA; Smith, E; Becker, EL. (1975) The isolation and partial characterization of neutrophil chemotactic factors from Escherichia coli. J. Immunol., 114 (6): 1831-7. [PMID:165239]

72. Schreiber, RE; Prossnitz, ER; Ye, RD; Cochrane, CG; Jesaitis, AJ; Bokoch, GM. (1993) Reconstitution of recombinant N-formyl chemotactic peptide receptor with G protein. J. Leukoc. Biol., 53 (4): 470-4. [PMID:8482927]

73. Seifert, R; Wenzel-Seifert, K. (2001) Defective Gi protein coupling in two formyl peptide receptor mutants associated with localized juvenile periodontitis. J. Biol. Chem., 276 (45): 42043-9. [PMID:11559706]

74. Sergeant, S; McPhail, LC. (2007) Measurement of phospholipid metabolism in intact neutrophils. Methods Mol. Biol., 412: 69-83. [PMID:18453106]

75. Sharma, VP; DesMarais, V; Sumners, C; Shaw, G; Narang, A. (2008) Immunostaining evidence for PI(4,5)P2 localization at the leading edge of chemoattractant-stimulated HL-60 cells. J. Leukoc. Biol., 84 (2): 440-7. [PMID:18477691]

76. Showell, H.J., Freer, R.J., Zigmond, S.H., Schiffmann, E., Aswanikumar, S., Corcoran, B. and Becker, E.L. (1976) The structure-activity relations of synthetic peptides as chemotactic factors and inducers of lysosomal secretion for neutrophils. J Exp Med., 143: 1154-1169. [PMID:1262785]

77. Southgate, EL; He, RL; Gao, JL; Murphy, PM; Nanamori, M; Ye, RD. (2008) Identification of formyl peptides from Listeria monocytogenes and Staphylococcus aureus as potent chemoattractants for mouse neutrophils. J. Immunol., 181 (2): 1429-37. [PMID:18606697]

78. Su, SB; Gong, WH; Gao, JL; Shen, WP; Grimm, MC; Deng, X; Murphy, PM; Oppenheim, JJ; Wang, JM. (1999) T20/DP178, an ectodomain peptide of human immunodeficiency virus type 1 gp41, is an activator of human phagocyte N-formyl peptide receptor. Blood, 93 (11): 3885-92. [PMID:10339497]

79. Sun, R., Iribarren, P., Zhang, N., Zhou, Y., Gong, W., Cho, E.H., Lockett, S., Chertov, O., Bednar, F., Rogers, T.J., Oppenheim, J.J. and Wang, J.M. (2004) Identification of neutrophil granule protein cathepsin G as a novel chemotactic agonist for the G protein-coupled formyl peptide receptor. J. Immunology, 173: 428-436. [PMID:15210802]

80. Takenawa, T; Ishitoya, J; Homma, Y; Kato, M; Nagai, Y. (1985) Role of enhanced inositol phospholipid metabolism in neutrophil activation. Biochem. Pharmacol., 34 (11): 1931-5. [PMID:2988563]

81. Unitt, J; Fagura, M; Phillips, T; King, S; Perry, M; Morley, A; MacDonald, C; Weaver, R; Christie, J; Barber, S; et al.. (2011) Discovery of small molecule human FPR1 receptor antagonists. Bioorg. Med. Chem. Lett., 21 (10): 2991-7. [PMID:21486695]

82. Walther, A., Riehemann, K. and Gerke, V. (2000) A novel ligand of the formyl peptide receptor: annexin I regulates neutrophil extravasation by interacting with the FPR. Mol Cell., 5: 831-840. [PMID:10882119]

83. Wenzel-Seifert, K., Grünbaum, L. and Seifert, R. (1991) Differential inhibition of human neutrophil activation by cyclosporins A, D, and H. Cyclosporin H is a potent and effective inhibitor of formyl peptide-induced superoxide formation. J. Immunology, 147: 1940-1946. [PMID:1653806]

84. Wenzel-Seifert, K; Seifert, R. (1993) Cyclosporin H is a potent and selective formyl peptide receptor antagonist. Comparison with N-t-butoxycarbonyl-L-phenylalanyl-L-leucyl-L-phenylalanyl-L- leucyl-L-phenylalanine and cyclosporins A, B, C, D, and E. J. Immunol., 150 (10): 4591-9. [PMID:8387097]

85. Williams, LT; Snyderman, R; Pike, MC; Lefkowitz, RJ. (1977) Specific receptor sites for chemotactic peptides on human polymorphonuclear leukocytes. Proc. Natl. Acad. Sci. U.S.A., 74 (3): 1204-8. [PMID:265563]

86. Yamamoto, Y., Kanazawa, T., Shimamura, M., Ueki, M. and Hazato, T. (1997) Inhibitory effects of spinorphin, a novel endogenous regulator, on chemotaxis, O2- generation, and exocytosis by N-formylmethionyl-leucyl-phenylalanine (FMLP)-stimulated neutrophils. Biochem Pharmacol, 54: 695-701. [PMID:9310346]

87. Yan, P., Nanamori, M., Sun, M., Zhou, C., Cheng, N., Li, N., Zheng, W., Xiao, L., Xie, X., Ye, R.D. and Wang, M.W. (2006) The immunosuppressant cyclosporin A antagonizes human formyl peptide receptor through inhibition of cognate ligand binding. J Immunology, 177: 7050-7058. [PMID:17082621]

88. Young, SM; Bologa, C; Prossnitz, ER; Oprea, TI; Sklar, LA; Edwards, BS. (2005) High-throughput screening with HyperCyt flow cytometry to detect small molecule formylpeptide receptor ligands. J Biomol Screen, 10 (4): 374-82. [PMID:15964939]

89. Zigmond, SH. (1977) Ability of polymorphonuclear leukocytes to orient in gradients of chemotactic factors. J. Cell Biol., 75 (2 Pt 1): 606-16. [PMID:264125]

To cite this database page, please use the following:

Formylpeptide receptors: FPR1. Last modified on 07/03/2013. Accessed on 26/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=222.


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