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Gene Review

FPR2  -  formyl peptide receptor 2

Homo sapiens

Synonyms: ALXR, FMLP-R-I, FMLP-R-II, FMLP-related receptor I, FMLPX, ...
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Disease relevance of FPRL1

  • As a novel described FPRL1 antagonist, it might lead to the development of therapeutic agents in FPRL1-mediated inflammatory components of diseases such as systemic amyloidosis, Alzheimer's, and prion disease [1].
  • These observations indicate that the binding of SAA to FPRL1 may contribute to the destruction of bone and cartilage via the promotion of synoviocyte hyperplasia and angiogenesis, thus providing a potential target for the control of RA [2].
  • The cecropin-like bactericidal peptide Hp(2-20) from Helicobacter pylori induces activation of the NADPH oxidase in human neutrophils via formyl peptide receptor-like 1 (FPRL1) (J. Bylund, T. Christophe, F. Boulay, T. Nyström, A. Karlsson, and C. Dahlgren, Antimicrob. Agents Chemother. 45:1700-1704, 2001) [3].
  • Considering the potential importance of FPRL1 in inflammation and neurodegenerative diseases, the identification of functional domains in this receptor will provide valuable information for the design of specific receptor antagonists [4].
  • These results demonstrate that activation of FPRL1 on human moncytes by a peptide domain derived from HIV-1 gp120 could lead to desensitization of cell response to other chemoattractants [5].

Psychiatry related information on FPRL1

  • 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].

High impact information on FPRL1

  • Together, these results indicate functional redundancies in endogenous lipid and peptide anti-inflammatory circuits that are spatially and temporally separate, where both ATL and specific ANXA1-derived peptides act in concert at ALXR to downregulate PMN recruitment to inflammatory loci [7].
  • Here, we report that inhibition of PMN infiltration by ASA and DEX is a property shared by aspirin-triggered lipoxins (ATL) and the glucocorticoid-induced annexin 1 (ANXA1)-derived peptides that are both generated in vivo and act at the lipoxin A(4) receptor (ALXR/FPRL1) to halt PMN diapedesis [7].
  • LL-37-induced Ca(2+) mobilization in monocytes can also be cross-desensitized by an FPRL1-specific agonist [8].
  • Moreover, they suggest that ALXR activation by LX or ATL can protect the host from potentially deleterious PMN responses associated with innate immunity as well as direct effector responses in tissue injury by recognition of peptide fragments [9].
  • Our results suggest that FPRL1 mediates phagocyte migration in response to SAA [10].

Chemical compound and disease context of FPRL1


Biological context of FPRL1


Anatomical context of FPRL1

  • We now describe a new protein from S. aureus that impaired the neutrophil responses to FPR-like1 (FPRL1) agonists [1].
  • Our study suggests that FPR and FPRL1 in phagocytes react to a broad spectrum of agonists and WKYMVm as a remarkably potent agonist provides a valuable tool for studying leukocyte signaling via these receptors [18].
  • RESULTS: A-SAA messenger RNA (mRNA) and FPRL1 mRNA were present in FLS, macrophages, and endothelial cells isolated from the synovial tissue of patients with RA and other categories of inflammatory arthritis [15].
  • Taken together, the results indicate that neutrophils are activated by WKYMVM through FPRL1 and that FPRL2 is a chemotactic receptor transducing signals in myeloid cells [19].
  • A-SAA expression was regulated by proinflammatory cytokines and occurred in association with FPRL1 expression in FLS and endothelial cells, which is consistent with a biologic role at the sites of inflammation [15].

Associations of FPRL1 with chemical compounds

  • While FPRL1-expressing cells migrated to picomolar concentrations of WKYMVm, nanomolar concentrations of the peptide were required to induce migration of FPR-expressing cells [18].
  • FPRL1 displays a large array of exogenous and endogenous ligands, including the chemokine variant sCKbeta8-1, the neuroprotective peptide humanin, and lipoxin A4 [20].
  • Metabolic labeling with orthophosphoric acid revealed that FPRL1 was differentially phosphorylated upon addition of the l- or d-conformer, indicating that it induced different conformational changes [19].
  • Among several FPRL1 agonists, including Trp-Lys-Tyr-Met-Val-D-Met (WKYMVm), SAA selectively stimulated MMP-9 upregulation [21].
  • Our data suggest that histamine downregulates FPRL1- and FPR-induced NADPH oxidase activity upstream of protein kinase C (PKC) and downstream of the separation of the peptide-induced signal into granule secretion and oxidase activation [22].

Physical interactions of FPRL1


Enzymatic interactions of FPRL1

  • Activation of the chemotactic peptide receptor FPRL1 in monocytes phosphorylates the chemokine receptor CCR5 and attenuates cell responses to selected chemokines [26].

Regulatory relationships of FPRL1


Other interactions of FPRL1

  • FPRL1 cDNA encodes a 351-amino acid polypeptide whose sequence is 69% identical to that of FPR [16].
  • Therapeutic targeting of A-SAA, or FPRL1, may modulate pathophysiologic pathways that are associated with matrix degradation in patients with RA and other forms of progressive inflammatory arthritis [15].
  • Furthermore, a cleavage fragment of neutrophil granule-derived bactericidal cathelicidin, LL-37, is also a chemotactic agonist for FPRL1 [29].
  • Formyl peptide receptor-like 1 (FPRL1) is a seven transmembrane domain, G protein-coupled receptor that interacts with a variety of exogenous and host-derived agonists [4].
  • These results indicate that heterologous desensitization of CCR5 and CXCR4 by an FPRL1 agonist attenuates their major biologic functions and suggest an approach to the development of additional anti-HIV-1 agents [27].

Analytical, diagnostic and therapeutic context of FPRL1


  1. 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]
  2. Serum amyloid a binding to formyl Peptide receptor-like 1 induces synovial hyperplasia and angiogenesis. Lee, M.S., Yoo, S.A., Cho, C.S., Suh, P.G., Kim, W.U., Ryu, S.H. J. Immunol. (2006) [Pubmed]
  3. Lipopolysaccharide-induced granule mobilization and priming of the neutrophil response to Helicobacter pylori peptide Hp(2-20), which activates formyl peptide receptor-like 1. Bylund, J., Karlsson, A., Boulay, F., Dahlgren, C. Infect. Immun. (2002) [Pubmed]
  4. Identification of functional domains in the formyl peptide receptor-like 1 for agonist-induced cell chemotaxis. Le, Y., Ye, R.D., Gong, W., Li, J., Iribarren, P., Wang, J.M. FEBS J. (2005) [Pubmed]
  5. 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. Deng, X., Ueda, H., Su, S.B., Gong, W., Dunlop, N.M., Gao, J.L., Murphy, P.M., Wang, J.M. Blood (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. Endogenous lipid- and peptide-derived anti-inflammatory pathways generated with glucocorticoid and aspirin treatment activate the lipoxin A4 receptor. Perretti, M., Chiang, N., La, M., Fierro, I.M., Marullo, S., Getting, S.J., Solito, E., Serhan, C.N. Nat. Med. (2002) [Pubmed]
  8. LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. De Yang, n.u.l.l., Chen, Q., Schmidt, A.P., Anderson, G.M., Wang, J.M., Wooters, J., Oppenheim, J.J., Chertov, O. J. Exp. Med. (2000) [Pubmed]
  9. Activation of lipoxin A(4) receptors by aspirin-triggered lipoxins and select peptides evokes ligand-specific responses in inflammation. Chiang, N., Fierro, I.M., Gronert, K., Serhan, C.N. J. Exp. Med. (2000) [Pubmed]
  10. 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]
  11. Activation of formyl peptide receptor-like 1 by WKYMVm induces serine phosphorylation of STAT3, which inhibits its tyrosine phosphorylation and nuclear translocation induced by hydrogen peroxide. Jo, E.J., Lee, H.Y., Kim, J.I., Kang, H.K., Lee, Y.N., Kwak, J.Y., Bae, Y.S. Life Sci. (2004) [Pubmed]
  12. 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]
  13. Expression of functional formyl peptide receptors by human astrocytoma cell lines. Le, Y., Hu, J., Gong, W., Shen, W., Li, B., Dunlop, N.M., Halverson, D.O., Blair, D.G., Wang, J.M. J. Neuroimmunol. (2000) [Pubmed]
  14. Orally administered FPRL1 receptor agonist peptide MMK-1 inhibits etoposide-induced alopecia by a mechanism different from intraperitoneally administered MMK-1. Tsuruki, T., Yoshikawa, M. Peptides (2006) [Pubmed]
  15. Local expression of the serum amyloid A and formyl peptide receptor-like 1 genes in synovial tissue is associated with matrix metalloproteinase production in patients with inflammatory arthritis. O'Hara, R., Murphy, E.P., Whitehead, A.S., FitzGerald, O., Bresnihan, B. Arthritis Rheum. (2004) [Pubmed]
  16. 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]
  17. 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]
  18. 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]
  19. The synthetic peptide Trp-Lys-Tyr-Met-Val-Met-NH2 specifically activates neutrophils through FPRL1/lipoxin A4 receptors and is an agonist for the orphan monocyte-expressed chemoattractant receptor FPRL2. Christophe, T., Karlsson, A., Dugave, C., Rabiet, M.J., Boulay, F., Dahlgren, C. J. Biol. Chem. (2001) [Pubmed]
  20. 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]
  21. Serum amyloid A stimulates matrix-metalloproteinase-9 upregulation via formyl peptide receptor like-1-mediated signaling in human monocytic cells. Lee, H.Y., Kim, M.K., Park, K.S., Bae, Y.H., Yun, J., Park, J.I., Kwak, J.Y., Bae, Y.S. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  22. Histamine inhibits neutrophil NADPH oxidase activity triggered by the lipoxin A4 receptor-specific peptide agonist Trp-Lys-Tyr-Met-Val-Met. Betten, A., Dahlgren, C., Hermodsson, S., Hellstrand, K. Scand. J. Immunol. (2003) [Pubmed]
  23. Amyloid beta-peptide interactions with neuronal and glial cell plasma membrane: binding sites and implications for Alzheimer's disease. Verdier, Y., Zarándi, M., Penke, B. J. Pept. Sci. (2004) [Pubmed]
  24. The soluble D2D3(88-274) fragment of the urokinase receptor inhibits monocyte chemotaxis and integrin-dependent cell adhesion. Furlan, F., Orlando, S., Laudanna, C., Resnati, M., Basso, V., Blasi, F., Mondino, A. J. Cell. Sci. (2004) [Pubmed]
  25. Humanin, a newly identified neuroprotective factor, uses the G protein-coupled formylpeptide receptor-like-1 as a functional receptor. Ying, G., Iribarren, P., Zhou, Y., Gong, W., Zhang, N., Yu, Z.X., Le, Y., Cui, Y., Wang, J.M. J. Immunol. (2004) [Pubmed]
  26. Activation of the chemotactic peptide receptor FPRL1 in monocytes phosphorylates the chemokine receptor CCR5 and attenuates cell responses to selected chemokines. Shen, W., Proost, P., Li, B., Gong, W., Le, Y., Sargeant, R., Murphy, P.M., Van Damme, J., Wang, J.M. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
  27. The synthetic peptide WKYMVm attenuates the function of the chemokine receptors CCR5 and CXCR4 through activation of formyl peptide receptor-like 1. Li, B.Q., Wetzel, M.A., Mikovits, J.A., Henderson, E.E., Rogers, T.J., Gong, W., Le, Y., Ruscetti, F.W., Wang, J.M. Blood (2001) [Pubmed]
  28. Chemotaxis and calcium responses of phagocytes to formyl peptide receptor ligands is differentially regulated by cyclic ADP ribose. Partida-Sánchez, S., Iribarren, P., Moreno-García, M.E., Gao, J.L., Murphy, P.M., Oppenheimer, N., Wang, J.M., Lund, F.E. J. Immunol. (2004) [Pubmed]
  29. Receptors for chemotactic formyl peptides as pharmacological targets. Le, Y., Yang, Y., Cui, Y., Yazawa, H., Gong, W., Qiu, C., Wang, J.M. Int. Immunopharmacol. (2002) [Pubmed]
  30. 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]
  31. Low-affinity receptor-mediated induction of superoxide by N-formyl-methionyl-leucyl-phenylalanine and WKYMVm in IMR90 human fibroblasts. Ammendola, R., Russo, L., De Felice, C., Esposito, F., Russo, T., Cimino, F. Free Radic. Biol. Med. (2004) [Pubmed]
  32. Beta amyloid peptide (Abeta42) is internalized via the G-protein-coupled receptor FPRL1 and forms fibrillar aggregates in macrophages. Yazawa, H., Yu, Z.X., Takeda, n.u.l.l., Le, Y., Gong, W., Ferrans, V.J., Oppenheim, J.J., Li, C.C., Wang, J.M. FASEB J. (2001) [Pubmed]
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