Formyl peptide receptor 2
Ensembl | |||||||||
---|---|---|---|---|---|---|---|---|---|
UniProt | |||||||||
RefSeq (mRNA) | |||||||||
RefSeq (protein) | |||||||||
Location (UCSC) | Chr 19: 51.75 – 51.77 Mb | Chr 17: 18.11 – 18.11 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
N-formyl peptide receptor 2 (FPR2) is a
Because of its interaction with lipoxin A4, FPR2 is also commonly named the ALX/FPR2 or just ALX receptor.Expression
The FPR2 receptor is expressed on human
Function
Many
Nomenclature
Confusingly, there are two "standard" nomenclatures for FPR receptors and their genes, the first used, FPR, FPR1, and FPR2 and its replacement, FPR1, FPR2, and FPR3. The latter nomenclature is recommended by the International Union of Basic and Clinical Pharmacology[17] and is used here. Other previously used names for FPR1 are NFPR, and FMLPR; for FPR2 are FPRH1, FPRL1, RFP, LXA4R, ALXR, FPR2/ALX, HM63, FMLPX, and FPR2A; and for FPR3 are FPRH2, FPRL2, and FMLPY.[17]
Genes
Human
The human FPR2 gene encodes the 351 amino acid receptor, FPR2, within an intronless
Mouse
Mice have no less than 7 FPR receptors encoded by 7 genes that localize to chromosome 17A3.2 in the following order: Fpr1, Fpr-rs2 (or fpr2), Fpr-rs1 (or LXA4R), Fpr-rs4, Fpr-rs7, Fpr-rs7, Fpr-rs6, and Fpr-rs3; this locus also contains Pseudogenes ψFpr-rs2 and ψFpr-rs3 (or ψFpr-rs5) which lie just after Fpr-rs2 and Fpr-rs1, respectively. The 7 mouse FPR receptors have ≥50% amino acid sequence identity with each other as well as with the three human FPR receptors.[20] Fpr2 and mFpr-rs1 bind with high affinity and respond to lipoxins but have little or no affinity for, and responsiveness to, formyl peptides; they thereby share key properties with human FPR2;[21][22][23]
Gene knockout studies
The large number of mouse compared to human FPR receptors makes it difficult to extrapolate human FPR functions based on genetic (e.g. gene knockout or forced overexpression) or other experimental manipulations of the FPR receptors in mice. In any event, combined disruption of the Fpr2 and Fpr3 genes causes mice to mount enhanced acute inflammatory responses as evidenced in three models, intestine inflammation caused by mesenteric artery ischemia-reperfusion, paw swelling caused by carrageenan injection, and arthritis caused by the intraperatoneal injection of arthritis-inducing serum.[24] Since Fpr2 gene knockout mice exhibit a faulty innate immune response to intravenous listeria monocytogenes injection,[25] these results suggest that the human FPR2 receptor and mouse Fpr3 receptor have equivalent functions in dampening at least certain inflammatory response.
Other species
Rats express an ortholog of FPR2 (74% amino acid sequence identity) with high affinity for
Cellular and tissue distribution
FPL2 is often co-expressed with FPR1. It is widely expressed by circulating blood
FPR2 is also known as the LXA4 or ALX/FPR2 receptor based on studies finding that is a high affinity receptor for the arachidonic acid metabolite, lipoxin A4 (LXA4), and thereafter for a related arachidonic acid metabolite, the Epi-lipoxin, aspirin-triggered lipoxin A4 (i.e. ATL, 15-epi-LXA4) and a docosahexaenoic acid metabolite, resolvin D1 (i.e. RvD1); these three cell-derived fatty acid metabolites act to inhibit and resolve inflammatory responses.[30][31][32][33][34] This receptor was previously known as an orphan receptor, termed RFP, obtained by screening myeloid cell-derived libraries with a FMLP-like probe.[35][36][37] In addition to LXA4, LTA, RvD1, and FMLP, FPR2 binds a wide range of polypeptides, proteins, and products derived from these polypeptides and proteins. One or more of these various ligands may be involved not only in regulating inflammation but also be involved in the development of obesity, cognitive decline, reproduction, neuroprotection, and cancer.[38] However, the most studied and accepted role for FPR2 receptors is in mediating the actions of the cited lipoxins and resolvins in dampening and resolving a wide range of inflammatory reactions (see lipoxin, Epi-lipoxin, and resolvin).[39][40]
The following is a list of FPR2/ALX ligands and in parentheses their suggested pro-inflammatory or anti-inflammatory actions base on in vitro and animal model studies: a) bacterial and mitochondrial N-formyl peptides such as FMLP (pro-inflammatory but perhaps less significant or insignificant compared to the actions of LXA4, ATL, and RvD1 on FPR2);
b) Hp(2-20), a non-formyl peptide derived from Helicobacter pylori (pro-inflammatory by promoting inflammatory responses against this stomach ulcer-causing pathogen);
c) T21/DP107 and N36, which are N-acetylated polypeptides derived from the gp41 envelope protein of the
d) the N-terminally truncated form of the chemotactic chemokine, CCL23, termed CCL23 splice variant CCL23β(amino acids 22–137) and SHAAGtide, which is a product of CCL23β cleavage by pro-inflammatory proteases (pro-inflammatory); e) two N-acetyl peptides, Ac2–26 and Ac9–25 of Annexin A1 (ANXA1 or lipocortin 1), which at high concentrations fully stimulate neutrophil functions but at lower concentrations leave neutrophils desensitized (i.e. unresponsive) to the chemokine IL-8 (CXCL8) (pro-inflammatory and anti-inflammatory, respectively, highlighting the duality of FPR2/ALX functions in inflammation);
f) Amyloid beta(1–42) fragment and prion protein fragment PrP(106–126) (pro-inflammatory, suggesting a role for FPR2/ALX in the inflammatory components of diverse amyloid-based diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, prion-based diseases such as Transmissible spongiform encephalopathy, Creutzfeldt–Jakob disease, and Kuru), and numerous other neurological and non-neurological diseases [see amyloid]);
g) the neuroprotective peptide, Humanin (anti-inflammatory by inhibiting the pro-inflammatory effects of Amalyoid beta(1-42) in promoting Alzheimer's disease-related inflammation);
h) two cleaved soluble fragments of
i) LL-37 and CRAMP, which are enzymatic cleavage products of human and rat, respectively,
j) Pituitary adenylate cyclase-activating polypeptide 27 (pro-inflammatory).[17][41]
See also
- Eicosanoid receptor
- Formyl peptide receptor
- Lipoxin
- Resolvin
- Formyl peptide receptor 1
- Formyl peptide receptor 3
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000171049 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000052270 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 9054386.
- ^ "Entrez Gene: FPR2 formyl peptide receptor 2".
- PMID 26546247.
- PMID 2832415.
- PMID 2161213.
- PMID 2176894.
- S2CID 22817786.
- PMID 2156834.
- PMID 1445895.
- PMID 1612600.
- PMID 1373134.
- PMID 1374236.
- ^ PMID 19498085.
- S2CID 24870278.
- S2CID 14266716.
- ^ PMID 17084101.
- PMID 23160941.
- PMID 9151906.
- PMID 12218158.
- PMID 20107188.
- PMID 23139859.
- PMID 15187157.
- PMID 17559171.
- S2CID 17721865.
- ^ S2CID 23300384.
- PMID 20080636.
- PMID 21724996.
- PMID 8389617.
- PMID 8006586.
- PMID 11141472.
- PMID 2176894.
- PMID 1373134.
- PMID 1511907.
- PMID 25857211.
- PMID 20526535.
- PMID 24656045.
- PMID 25791526.
Further reading
- Murphy PM, Ozçelik T, Kenney RT, Tiffany HL, McDermott D, Francke U (Apr 1992). "A structural homologue of the N-formyl peptide receptor. Characterization and chromosome mapping of a peptide chemoattractant receptor family". The Journal of Biological Chemistry. 267 (11): 7637–43. PMID 1373134.
- Ye RD, Cavanagh SL, Quehenberger O, Prossnitz ER, Cochrane CG (Apr 1992). "Isolation of a cDNA that encodes a novel granulocyte N-formyl peptide receptor". Biochemical and Biophysical Research Communications. 184 (2): 582–9. PMID 1374236.
- Perez HD, Holmes R, Kelly E, McClary J, Andrews WH (Sep 1992). "Cloning of a cDNA encoding a receptor related to the formyl peptide receptor of human neutrophils". Gene. 118 (2): 303–4. PMID 1511907.
- Bao L, Gerard NP, Eddy RL, Shows TB, Gerard C (Jun 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 (2): 437–40. PMID 1612600.
- Nomura H, Nielsen BW, Matsushima K (Oct 1993). "Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte chemotactic peptide receptors". PMID 7505609.
- Durstin M, Gao JL, Tiffany HL, McDermott D, Murphy PM (May 1994). "Differential expression of members of the N-formylpeptide receptor gene cluster in human phagocytes". Biochemical and Biophysical Research Communications. 201 (1): 174–9. PMID 8198572.
- Takano T, Fiore S, Maddox JF, Brady HR, Petasis NA, Serhan CN (May 1997). "Aspirin-triggered 15-epi-lipoxin A4 (LXA4) and LXA4 stable analogues are potent inhibitors of acute inflammation: evidence for anti-inflammatory receptors". The Journal of Experimental Medicine. 185 (9): 1693–704. PMID 9151906.
- Gronert K, Gewirtz A, Madara JL, Serhan CN (Apr 1998). "Identification of a human enterocyte lipoxin A4 receptor that is regulated by interleukin (IL)-13 and interferon gamma and inhibits tumor necrosis factor alpha-induced IL-8 release". The Journal of Experimental Medicine. 187 (8): 1285–94. PMID 9547339.
- Deng X, Ueda H, Su SB, Gong W, Dunlop NM, Gao JL, Murphy PM, Wang JM (Aug 1999). "A synthetic peptide derived from human immunodeficiency virus type 1 gp120 downregulates the expression and function of chemokine receptors CCR5 and CXCR4 in monocytes by activating the 7-transmembrane G-protein-coupled receptor FPRL1/LXA4R". Blood. 94 (4): 1165–73. PMID 10438703.
- Chiang N, Fierro IM, Gronert K, Serhan CN (Apr 2000). "Activation of lipoxin A(4) receptors by aspirin-triggered lipoxins and select peptides evokes ligand-specific responses in inflammation". The Journal of Experimental Medicine. 191 (7): 1197–208. PMID 10748237.
- Shen W, Proost P, Li B, Gong W, Le Y, Sargeant R, Murphy PM, Van Damme J, Wang JM (May 2000). "Activation of the chemotactic peptide receptor FPRL1 in monocytes phosphorylates the chemokine receptor CCR5 and attenuates cell responses to selected chemokines". Biochemical and Biophysical Research Communications. 272 (1): 276–83. PMID 10872839.
- Le Y, Jiang S, Hu J, Gong W, Su S, Dunlop NM, Shen W, Li B, Ming Wang J (Sep 2000). "N36, a synthetic N-terminal heptad repeat domain of the HIV-1 envelope protein gp41, is an activator of human phagocytes". Clinical Immunology. 96 (3): 236–42. PMID 10964542.
- Chen Q, Schmidt AP, Anderson GM, Wang JM, Wooters J, Oppenheim JJ, Chertov O (Oct 2000). "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". The Journal of Experimental Medicine. 192 (7): 1069–74. PMID 11015447.
- Kang Y, Taddeo B, Varai G, Varga J, Fiore S (Nov 2000). "Mutations of serine 236-237 and tyrosine 302 residues in the human lipoxin A4 receptor intracellular domains result in sustained signaling". Biochemistry. 39 (44): 13551–7. PMID 11063592.
- Svensson L, Dahlgren C, Wennerås C (Oct 2002). "The chemoattractant Trp-Lys-Tyr-Met-Val-D-Met activates eosinophils through the formyl peptide receptor and one of its homologues, formyl peptide receptor-like 1". Journal of Leukocyte Biology. 72 (4): 810–8. S2CID 45789067.
- He R, Sang H, Ye RD (Feb 2003). "Serum amyloid A induces IL-8 secretion through a G protein-coupled receptor, FPRL1/LXA4R". Blood. 101 (4): 1572–81. PMID 12393391.
- Christophe T, Karlsson A, Rabiet MJ, Boulay F, Dahlgren C (Nov 2002). "Phagocyte activation by Trp-Lys-Tyr-Met-Val-Met, acting through FPRL1/LXA4R, is not affected by lipoxin A4". Scandinavian Journal of Immunology. 56 (5): 470–6. PMID 12410796.
- Kucharzik T, Gewirtz AT, Merlin D, Madara JL, Williams IR (Apr 2003). "Lateral membrane LXA4 receptors mediate LXA4's anti-inflammatory actions on intestinal epithelium". American Journal of Physiology. Cell Physiology. 284 (4): C888-96. PMID 12456400.
- Qin CX, Norling LV, Vecchio EA, Brennan EP, May LT, Wootten D, Godson C, Perretti M, Ritchie RH (October 2022). "Formylpeptide receptor 2: Nomenclature, structure, signalling and translational perspectives: IUPHAR review 35". .
External links
- "Formylpeptide Receptors: FPRL1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.