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Gene Review

FPR1  -  formyl peptide receptor 1

Homo sapiens

Synonyms: FMLP, FPR, N-formyl peptide receptor, N-formylpeptide chemoattractant receptor, fMLP receptor, ...
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Disease relevance of FPR1


Psychiatry related information on FPR1

  • Human formyl peptide receptor (FPR)-like 1 (FPRL1) and its mouse homologue mFPR2 are functional receptors for a variety of exogenous and host-derived chemotactic peptides, including amyloid beta 1-42 (Abeta(42)), a pathogenic factor in Alzheimer's disease [6].
  • The degranulation response of human neutrophils to the calcium ionophore A23187, serum opsonized zymosan (ZC), aggregated gamma-globulin (A gamma G), C5a, formyl-methionyl-leucyl-phenylalanine (FMLP), and PMA has been studied as a reaction time course in order to compare the release kinetics of the separate granule types [7].
  • During daytime sleep the % FPR was significantly smaller in SWS than in stage 2 or REM sleep [8].

High impact information on FPR1


Chemical compound and disease context of FPR1

  • Treatment of endometrial adenocarcinoma explants with PGF(2 alpha) resulted in mobilization of inositol phosphate signaling, indicating functional FP receptor expression [13].
  • Of the latter compounds, compound 14 (1,3-benzodioxolane-5-carboxylic acid 4'-benzyloxy-3'-methoxybenzylidene-hydrazide) activated neutrophils at nanomolar concentrations, and Ca(2+) mobilization was inhibited by pertussis toxin and N-t-butoxycarbonyl-Phe-Leu-Phe-Leu-Phe (Boc-2), an antagonist of formyl peptide receptors (FPR/FPRL1) [14].
  • We investigated a role for PGF2alpha-FP receptor interaction in modulating COX-2 expression and PGF2alpha biosynthesis using an endometrial adenocarcinoma cell line stably transfected with the FP receptor cDNA (FPS cells) [15].
  • Platelet chemotaxis to formyl peptides was blocked with FPR-specific antibody as well as by pertussis toxin inhibition of the formyl peptide G-coupled receptor [16].
  • An FKBP-rapamycin complex is concluded to be the toxic agent because (i) strains that lack FKBP proline rotamase, encoded by FPR1, were viable and fully resistant to rapamycin and (ii) FK506 antagonized rapamycin toxicity in vivo [10].

Biological context of FPR1

  • The high-affinity fMLP receptor (FPR1) of phagocytic cells interacts with bacterial fMLP and mediates chemotaxis, degranulation, and superoxide production [1].
  • To evaluate the generality of these SNPs in AP patients, we sequenced a 363 bp interval of the FPR1 gene in an ethnically diverse group of patients (n=111) and controls (n=115) [1].
  • Six SNPs were identified including two located in the FPR1 second extracellular loop that were significantly associated with the AP phenotype in African-American patients (p.R190W, P=0.0033; and p.N192K, P=0.0018) [1].
  • We found that the FPR1 polymorphisms are linked in 15 common haplotypes [17].
  • Thus, the regulation of FPRL2 gene expression in vivo differs from FPR1 and FPRL1 [18].

Anatomical context of FPR1

  • These results suggest that FPR1 may be the only gene that is expressed by neutrophils that encodes a receptor capable of binding prototype N-formyl peptides [19].
  • The human genes for two N-formylpeptide phagocyte chemoattractant receptors (gene symbols FPR1 and FPRL1) cross-hybridize with each other and with FPRL2, a human gene of unknown expression and function [18].
  • The annexin 1 peptide initiates chemotactic responses in human monocytes that express all three FPR family members and also desensitizes the cells toward subsequent stimulation with bacterial peptide agonists [4].
  • Preincubation of basophils with FMLP or Hp(2-20) caused complete desensitization to a subsequent challenge with homologous stimulus [20].
  • This first report of a functional formyl peptide receptor in cells of fibroblast origin opens new possibilities for the role of fibroblasts in innate immune responses [21].

Associations of FPR1 with chemical compounds


Physical interactions of FPR1


Regulatory relationships of FPR1

  • These observations identify the annexin 1 peptide as the first endogenous ligand of FPRL2 and indicate that annexin 1 participates in regulating leukocyte emigration into inflamed tissue by activating and desensitizing different receptors of the FPR family [4].
  • Analogs with substitution at the third position such as WKGMVm, WKRMVm, as well as analogs with substitution at the sixth d-Met, selectively altered calcium mobilization in cells expressing FPRL1 but not in cells expressing FPR [31].
  • Here we show that triggering of the formyl peptide receptor (FPR) with f-Met-Leu-Phe (fMLF) substantially reduced the neutrophil superoxide production induced by activation of the CXC receptors with IL-8 [32].
  • FMLP-stimulated CD11b upregulation as well as homotypic aggregation of PMN was inhibited by LXA4 (which at 10(-9) M gave approximately 1 log unit shift to the right in the FMLP dose-response curve) [33].
  • In contrast, the specific mRNA for the FMLP receptor, 3H-FMLP specific binding, and FMLP-induced phospholipase D activity were still observed [33].

Other interactions of FPR1


Analytical, diagnostic and therapeutic context of FPR1


  1. Evaluation of human leukocyte N-formylpeptide receptor (FPR1) SNPs in aggressive periodontitis patients. Zhang, Y., Syed, R., Uygar, C., Pallos, D., Gorry, M.C., Firatli, E., Cortelli, J.R., VanDyke, T.E., Hart, P.S., Feingold, E., Hart, T.C. Genes Immun. (2003) [Pubmed]
  2. The rabbit neutrophil N-formyl peptide receptor. cDNA cloning, expression, and structure/function implications. Ye, R.D., Quehenberger, O., Thomas, K.M., Navarro, J., Cavanagh, S.L., Prossnitz, E.R., Cochrane, C.G. J. Immunol. (1993) [Pubmed]
  3. A new staphylococcal anti-inflammatory protein that antagonizes the formyl Peptide receptor-like 1. Prat, C., Bestebroer, J., de Haas, C.J., van Strijp, J.A., van Kessel, K.P. J. Immunol. (2006) [Pubmed]
  4. An annexin 1 N-terminal peptide activates leukocytes by triggering different members of the formyl peptide receptor family. Ernst, S., Lange, C., Wilbers, A., Goebeler, V., Gerke, V., Rescher, U. J. Immunol. (2004) [Pubmed]
  5. T21/DP107, A synthetic leucine zipper-like domain of the HIV-1 envelope gp41, attracts and activates human phagocytes by using G-protein-coupled formyl peptide receptors. Su, S.B., Gao, J., Gong, W., Dunlop, N.M., Murphy, P.M., Oppenheim, J.J., Wang, J.M. J. Immunol. (1999) [Pubmed]
  6. Induction of the Formyl Peptide Receptor 2 in Microglia by IFN-{gamma} and Synergy with CD40 Ligand. Chen, K., Iribarren, P., Huang, J., Zhang, L., Gong, W., Cho, E.H., Lockett, S., Dunlop, N.M., Wang, J.M. J. Immunol. (2007) [Pubmed]
  7. The sequential release of granule constitutents from human neutrophils. Bentwood, B.J., Henson, P.M. J. Immunol. (1980) [Pubmed]
  8. Electroencephalogram and cardiovascular responses to noise during daytime sleep in shiftworkers. Nicolas, A., Bach, V., Tassi, P., Dewasmes, G., Ehrhart, J., Muzet, A., Libert, J.P. European journal of applied physiology and occupational physiology. (1993) [Pubmed]
  9. Carboxyl methylation of Ras-related proteins during signal transduction in neutrophils. Philips, M.R., Pillinger, M.H., Staud, R., Volker, C., Rosenfeld, M.G., Weissmann, G., Stock, J.B. Science (1993) [Pubmed]
  10. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Heitman, J., Movva, N.R., Hall, M.N. Science (1991) [Pubmed]
  11. Cloning of complementary DNA encoding a functional human interleukin-8 receptor. Murphy, P.M., Tiffany, H.L. Science (1991) [Pubmed]
  12. A seven-transmembrane, G protein-coupled receptor, FPRL1, mediates the chemotactic activity of serum amyloid A for human phagocytic cells. Su, S.B., Gong, W., Gao, J.L., Shen, W., Murphy, P.M., Oppenheim, J.J., Wang, J.M. J. Exp. Med. (1999) [Pubmed]
  13. Expression, localization, and signaling of prostaglandin F2 alpha receptor in human endometrial adenocarcinoma: regulation of proliferation by activation of the epidermal growth factor receptor and mitogen-activated protein kinase signaling pathways. Sales, K.J., Milne, S.A., Williams, A.R., Anderson, R.A., Jabbour, H.N. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  14. High-throughput screening for small-molecule activators of neutrophils: identification of novel N-formyl Peptide receptor agonists. Schepetkin, I.A., Kirpotina, L.N., Khlebnikov, A.I., Quinn, M.T. Mol. Pharmacol. (2007) [Pubmed]
  15. A positive feedback loop that regulates cyclooxygenase-2 expression and prostaglandin F2alpha synthesis via the F-series-prostanoid receptor and extracellular signal-regulated kinase 1/2 signaling pathway. Jabbour, H.N., Sales, K.J., Boddy, S.C., Anderson, R.A., Williams, A.R. Endocrinology (2005) [Pubmed]
  16. Human platelets exhibit chemotaxis using functional N-formyl peptide receptors. Czapiga, M., Gao, J.L., Kirk, A., Lekstrom-Himes, J. Exp. Hematol. (2005) [Pubmed]
  17. Contrasting evolution of the human leukocyte N-formylpeptide receptor subtypes FPR and FPRL1R. Sahagun-Ruiz, A., Colla, J.S., Juhn, J., Gao, J.L., Murphy, P.M., McDermott, D.H. Genes Immun. (2001) [Pubmed]
  18. Differential expression of members of the N-formylpeptide receptor gene cluster in human phagocytes. Durstin, M., Gao, J.L., Tiffany, H.L., McDermott, D., Murphy, P.M. Biochem. Biophys. Res. Commun. (1994) [Pubmed]
  19. A structural homologue of the N-formyl peptide receptor. Characterization and chromosome mapping of a peptide chemoattractant receptor family. Murphy, P.M., Ozçelik, T., Kenney, R.T., Tiffany, H.L., McDermott, D., Francke, U. J. Biol. Chem. (1992) [Pubmed]
  20. Basophils infiltrate human gastric mucosa at sites of Helicobacter pylori infection, and exhibit chemotaxis in response to H. pylori-derived peptide Hp(2-20). de Paulis, A., Prevete, N., Fiorentino, I., Walls, A.F., Curto, M., Petraroli, A., Castaldo, V., Ceppa, P., Fiocca, R., Marone, G. J. Immunol. (2004) [Pubmed]
  21. Expression and function of formyl peptide receptors on human fibroblast cells. VanCompernolle, S.E., Clark, K.L., Rummel, K.A., Todd, S.C. J. Immunol. (2003) [Pubmed]
  22. Activation of the mitogen-activated protein kinase pathway by fMet-leu-Phe in the absence of Lyn and tyrosine phosphorylation of SHC in transfected cells. Torres, M., Ye, R.D. J. Biol. Chem. (1996) [Pubmed]
  23. Formyl peptide receptors are coupled to multiple mitogen-activated protein kinase cascades by distinct signal transduction pathways: role in activation of reduced nicotinamide adenine dinucleotide oxidase. Rane, M.J., Carrithers, S.L., Arthur, J.M., Klein, J.B., McLeish, K.R. J. Immunol. (1997) [Pubmed]
  24. Formyl peptide receptors: A promiscuous subfamily of G protein-coupled receptors controlling immune responses. Migeotte, I., Communi, D., Parmentier, M. Cytokine Growth Factor Rev. (2006) [Pubmed]
  25. 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. Le, Y., Gong, W., Li, B., Dunlop, N.M., Shen, W., Su, S.B., Ye, R.D., Wang, J.M. J. Immunol. (1999) [Pubmed]
  26. Formyl peptide receptor-1 activation enhances intestinal epithelial cell restitution through phosphatidylinositol 3-kinase-dependent activation of Rac1 and Cdc42. Babbin, B.A., Jesaitis, A.J., Ivanov, A.I., Kelly, D., Laukoetter, M., Nava, P., Parkos, C.A., Nusrat, A. J. Immunol. (2007) [Pubmed]
  27. Chemoattractant cross-desensitization of the human neutrophil IL-8 receptor involves receptor internalization and differential receptor subtype regulation. Sabroe, I., Williams, T.J., Hébert, C.A., Collins, P.D. J. Immunol. (1997) [Pubmed]
  28. Peptides derived from HIV-1, HIV-2, Ebola virus, SARS coronavirus and coronavirus 229E exhibit high affinity binding to the formyl peptide receptor. Mills, J.S. Biochim. Biophys. Acta (2006) [Pubmed]
  29. Dexras1/AGS-1 inhibits signal transduction from the Gi-coupled formyl peptide receptor to Erk-1/2 MAP kinases. Graham, T.E., Prossnitz, E.R., Dorin, R.I. J. Biol. Chem. (2002) [Pubmed]
  30. Formyl peptide receptor signaling in HL-60 cells through sphingosine kinase. Alemany, R., Meyer zu Heringdorf, D., van Koppen, C.J., Jakobs, K.H. J. Biol. Chem. (1999) [Pubmed]
  31. Differential activation of formyl peptide receptor signaling by peptide ligands. Bae, Y.S., Song, J.Y., Kim, Y., He, R., Ye, R.D., Kwak, J.Y., Suh, P.G., Ryu, S.H. Mol. Pharmacol. (2003) [Pubmed]
  32. The mechanism for activation of the neutrophil NADPH-oxidase by the peptides formyl-Met-Leu-Phe and Trp-Lys-Tyr-Met-Val-Met differs from that for interleukin-8. Fu, H., Bylund, J., Karlsson, A., Pellmé, S., Dahlgren, C. Immunology (2004) [Pubmed]
  33. Lipoxin A4 receptor activation is distinct from that of the formyl peptide receptor in myeloid cells: inhibition of CD11/18 expression by lipoxin A4-lipoxin A4 receptor interaction. Fiore, S., Serhan, C.N. Biochemistry (1995) [Pubmed]
  34. Identification of surrogate agonists for the human FPRL-1 receptor by autocrine selection in yeast. Klein, C., Paul, J.I., Sauvé, K., Schmidt, M.M., Arcangeli, L., Ransom, J., Trueheart, J., Manfredi, J.P., Broach, J.R., Murphy, A.J. Nat. Biotechnol. (1998) [Pubmed]
  35. The synthetic peptide Trp-Lys-Tyr-Met-Val-D-Met inhibits human monocyte-derived dendritic cell maturation via formyl peptide receptor and formyl peptide receptor-like 2. Kang, H.K., Lee, H.Y., Kim, M.K., Park, K.S., Park, Y.M., Kwak, J.Y., Bae, Y.S. J. Immunol. (2005) [Pubmed]
  36. 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. Bao, L., Gerard, N.P., Eddy, R.L., Shows, T.B., Gerard, C. Genomics (1992) [Pubmed]
  37. Urokinase induces basophil chemotaxis through a urokinase receptor epitope that is an endogenous ligand for formyl peptide receptor-like 1 and -like 2. de Paulis, A., Montuori, N., Prevete, N., Fiorentino, I., Rossi, F.W., Visconte, V., Rossi, G., Marone, G., Ragno, P. J. Immunol. (2004) [Pubmed]
  38. Isolation of a cDNA that encodes a novel granulocyte N-formyl peptide receptor. Ye, R.D., Cavanagh, S.L., Quehenberger, O., Prossnitz, E.R., Cochrane, C.G. Biochem. Biophys. Res. Commun. (1992) [Pubmed]
  39. The receptor for urokinase-type plasminogen activator and urokinase is translocated from two distinct intracellular compartments to the plasma membrane on stimulation of human neutrophils. Plesner, T., Ploug, M., Ellis, V., Rønne, E., Høyer-Hansen, G., Wittrup, M., Pedersen, T.L., Tscherning, T., Danø, K., Hansen, N.E. Blood (1994) [Pubmed]
  40. Simultaneous mobilization of Mac-1 (CD11b/CD18) and formyl peptide chemoattractant receptors in human neutrophils. Graves, V., Gabig, T., McCarthy, L., Strour, E.F., Leemhuis, T., English, D. Blood (1992) [Pubmed]
  41. Phosphorylation of the N-formyl peptide receptor carboxyl terminus by the G protein-coupled receptor kinase, GRK2. Prossnitz, E.R., Kim, C.M., Benovic, J.L., Ye, R.D. J. Biol. Chem. (1995) [Pubmed]
  42. C5a as a model for chemotactic factor-stimulated tyrosine phosphorylation in the human neutrophil. Richard, S., Farrell, C.A., Shaw, A.S., Showell, H.J., Connelly, P.A. J. Immunol. (1994) [Pubmed]
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