Formyl peptide receptor 1
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Location (UCSC) | Chr 19: 51.75 – 51.8 Mb | Chr 17: 18.1 – 18.1 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
Formyl peptide receptor 1 (FPR1, FPR1 receptor, fMet-Leu-Phe receptor 1, FMLP receptor 1, or N-formylmethionyl-leucyl-phenylalanine receptor 1) is a
Humans also express two
Function
FPR1 binds with and is activated by:
- bacterial and mitochondrial N-formyl peptides and thereby initiates innate host immune responses.
- various synthetic N-formyl and non-formylated peptides that show distinguishing differences from those that interact with FPR2 and FPR3.
- T20/DP178 & T21/DP107, N-acetylated polypeptides derived from the HIV-1 envelope protein. This interaction is of unknown physiological significance although peptide T20/DP178 is a licensed anti-retrovirus agent (pentafuside) termed Enfuvirtidewhich acts at the level of HIV-target cell fusion and is used clinically to treat HIV-1 infection).
- Annexin A1 (also termed ANXA1 and lipocortin 1) and its N-terminal peptides (Ac2–26 and Ac9–25). At low concentrations, these agents stimulate neutrophils to raise cytosolic Ca2+ levels and thereby activate Ca2+-dependent signaling pathways; however, they do not fully activate the MAPK pathway but rather leave the neutrophil desensitized (i.e. unresponsive) to chemokine IL-8. At high concentrations, in contrast, the agents fully activate neutrophils and are potent pro-inflammatory stimulants.[7]
History
Studies conducted in the 1970s found that a series of
Nomenclature
Confusingly, there are two nomenclatures for FPR receptors and their genes, the first one used, FPR, FPR1, and FPR2, and its replacement (which corresponds directly to these three respective receptors and their genes), FPR1, FPR2, and FPR3. The latter nomenclature was recommended by the International Union of Basic and Clinical Pharmacology[7] 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, FPR2A, and ALX/FPR2 (most recently, ALX/FPR2 is commonly used for FPR2); and for FPR3 are FPRH2, FPRL2, and FMLPY.[7]
Gene
Human
In early studies, cultured human
Mouse
Mouse formyl peptide receptor genes localize to chromosome 17A3.2 in the following order: Fpr1, Fpr-rs2 (or fpr2), Fpr-rs1 (or Lxa4R), Fpr-rs4, Fpr-rs7, Fpr-rs6, and Fpr-rs3; Pseudogenes ψFpr-rs2 and ψFpr-rs3 (or ψFpr-rs5) lie just after Fpr-rs2 and Fpr-rs1, respectively. All of the active mouse FPR receptors have ≥50% amino acid sequence identity with each other as well as with the three human FPR receptors.[6] Studies find that: a) mouse Fpr1 is an ortholog of human FPR1, responding to many bacterial- and mitochondrial-derived formyl peptides but only minimally to FMLP and having certain pharmacologic properties in common with human FPR2/ALX; b) mouse Fpr2 and mFpr-rs1 bind with high affinity and respond to lipoxins but have little affinity for or responsiveness to formyl peptides and therefore share key properties with human FPR2/ALX; and c) based on its predominantly intracellular distribution, mFpr-rs1 correlates, and therefore may share functionally, with human FPR3;[23][24][25]
The ψFpr-rs2 gene contains a deletion and frame shift which renders its protein 186 nucleotides shorter but 98% identical to the protein encoded by its closest paralog gene, Fpr-rs2. Since ψFpr-rs2 transcripts are expressed and inducible in multiple mouse tissues and since gene knockout studies ascribe functionality to it, ψFpr-rs2 may not a true pseudogene and, it is suggested, should be renamed Fpr-rs8.[26]
Fpr-rs1, Fpr-rs3, Fpr-rs4, Fpr-rs6, and Fpr-rs7 receptors are expressed in the olfactory bulb sensory neurons of the Vomeronasal organ where they have been shown to respond to their known ligands, FMLP and lipoxin A4. Isolated mouse Olfactory bulb neurons also respond to a range of other fpr agonists. These results suggest that the cited receptors function to allow the olfactory-based detection of various contaminated compounds such as spoiled food and/or their many inflammation-regulating and other agonists in bodily secretions.[27]
Gene knockout studies
The large number of mouse compared to human FPR receptors makes it difficult to extrapolate human FPR1 functions based on genetic (e.g. gene knockout or forced overexpression) or other experimental manipulations of FPR receptors in mice. In any event, targeted disruption of the Fpr1 gene reduced the ability of mice to survive intravenous injection of the bacterial pathogen, listeria monocytogenes;[28] disruption of the Fpr2 gene in mice produce a similar effect while disruption of both genes further lowered the survival of mice to the listeria challenge.[29] The effect of these gene knockouts appeared due to faulty leukocyte function and other causes leading to a breakdown in the innate immune response. The functions of the human FPR1 receptor may be equivalent to the overlapping functions of the mouse Fpr1 and Fpr2 functions and therefore be critical in the defense against at least certain bacteria. Targeted disruption of FPR-rs1 produced a 33% reduction in the lifetime of mice; there was no specific pathology associated with this reduction.[26]
Other species
FPR receptors are widely distributed throughout mammalian species with the FPR1, FPR2, and FPR3
Cellular and tissue distribution
FPR1 is widely expressed by circulating blood
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000171051 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000045551 – 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.
- ^ a b "Entrez Gene: Formyl peptide receptor 1".
- ^ PMID 17084101.
- ^ PMID 19498085.
- PMID 2161213.
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- PMID 2832415.
- PMID 2161213.
- PMID 2176894.
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- ^ S2CID 24870278.
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- ^ PMID 21691049.
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- S2CID 14266716.
- PMID 15187157.
- S2CID 29548200.
- S2CID 17721865.
Further reading
- Graves V, Gabig T, McCarthy L, Strour EF, Leemhuis T, English D (Aug 1992). "Simultaneous mobilization of Mac-1 (CD11b/CD18) and formyl peptide chemoattractant receptors in human neutrophils". Blood. 80 (3): 776–87. PMID 1322204.
- 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.
- Perez HD, Holmes R, Kelly E, McClary J, Chou Q, Andrews WH (Nov 1992). "Cloning of the gene coding for a human receptor for formyl peptides. Characterization of a promoter region and evidence for polymorphic expression". Biochemistry. 31 (46): 11595–9. PMID 1445895.
- 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.
- Murphy PM, McDermott D (Jul 1991). "Functional expression of the human formyl peptide receptor in Xenopus oocytes requires a complementary human factor". The Journal of Biological Chemistry. 266 (19): 12560–7. PMID 1712023.
- Boulay F, Tardif M, Brouchon L, Vignais P (Dec 1990). "The human N-formylpeptide receptor. Characterization of two cDNA isolates and evidence for a new subfamily of G-protein-coupled receptors". Biochemistry. 29 (50): 11123–33. PMID 2176894.
- Wahl SM, Allen JB, Gartner S, Orenstein JM, Popovic M, Chenoweth DE, Arthur LO, Farrar WL, Wahl LM (May 1989). "HIV-1 and its envelope glycoprotein down-regulate chemotactic ligand receptors and chemotactic function of peripheral blood monocytes". Journal of Immunology. 142 (10): 3553–9. S2CID 44347771.
- Jesaitis AJ, Naemura JR, Painter RG, Sklar LA, Cochrane CG (Dec 1982). "Intracellular localization of N-formyl chemotactic receptor and Mg2+ dependent ATPase in human granulocytes". Biochimica et Biophysica Acta (BBA) - General Subjects. 719 (3): 556–68. PMID 6129903.
- Prossnitz ER, Kim CM, Benovic JL, Ye RD (Jan 1995). "Phosphorylation of the N-formyl peptide receptor carboxyl terminus by the G protein-coupled receptor kinase, GRK2". The Journal of Biological Chemistry. 270 (3): 1130–7. PMID 7836371.
- Klotz KN, Jesaitis AJ (Sep 1994). "Physical coupling of N-formyl peptide chemoattractant receptors to G protein is unaffected by desensitization". Biochemical Pharmacology. 48 (6): 1297–300. PMID 7945424.
- Bommakanti RK, Dratz EA, Siemsen DW, Jesaitis AJ (Nov 1994). "Characterization of complex formation between Gi2 and octyl glucoside solubilized neutrophil N-formyl peptide chemoattractant receptor by sedimentation velocity". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 1209 (1): 69–76. PMID 7947984.
- Murphy PM, Tiffany HL, McDermott D, Ahuja SK (Nov 1993). "Sequence and organization of the human N-formyl peptide receptor-encoding gene". Gene. 133 (2): 285–90. PMID 8224916.
- Jesaitis AJ, Erickson RW, Klotz KN, Bommakanti RK, Siemsen DW (Nov 1993). "Functional molecular complexes of human N-formyl chemoattractant receptors and actin". Journal of Immunology. 151 (10): 5653–65. S2CID 45748273.
- Särndahl E, Bokoch GM, Boulay F, Stendahl O, Andersson T (Jun 1996). "Direct or C5a-induced activation of heterotrimeric Gi2 proteins in human neutrophils is associated with interaction between formyl peptide receptors and the cytoskeleton". The Journal of Biological Chemistry. 271 (25): 15267–71. PMID 8663057.
- Maestes DC, Potter RM, Prossnitz ER (Oct 1999). "Differential phosphorylation paradigms dictate desensitization and internalization of the N-formyl peptide receptor". The Journal of Biological Chemistry. 274 (42): 29791–5. PMID 10514456.
- Liang TS, Wang JM, Murphy PM, Gao JL (Apr 2000). "Serum amyloid A is a chemotactic agonist at FPR2, a low-affinity N-formylpeptide receptor on mouse neutrophils". Biochemical and Biophysical Research Communications. 270 (2): 331–5. PMID 10753626.
- Luu NT, Rainger GE, Nash GB (Jun 2000). "Differential ability of exogenous chemotactic agents to disrupt transendothelial migration of flowing neutrophils". Journal of Immunology. 164 (11): 5961–9. PMID 10820279.
- Bennett TA, Maestas DC, Prossnitz ER (Aug 2000). "Arrestin binding to the G protein-coupled N-formyl peptide receptor is regulated by the conserved "DRY" sequence". The Journal of Biological Chemistry. 275 (32): 24590–4. PMID 10823817.
- Ayala JM, Goyal S, Liverton NJ, Claremon DA, O'Keefe SJ, Hanlon WA (Jun 2000). "Serum-induced monocyte differentiation and monocyte chemotaxis are regulated by the p38 MAP kinase signal transduction pathway". Journal of Leukocyte Biology. 67 (6): 869–75. S2CID 28719955.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.