A structural homologue of the N-formyl peptide receptor. Characterization and chromosome mapping of a peptide chemoattractant receptor family.
Phagocytic cells of many higher species express calcium mobilizing G protein-coupled receptors for bacterial N-formyl peptides which mediate chemotaxis, degranulation, and the respiratory burst. cDNA encoding an N-formyl peptide receptor (FPR) has been reported. We now report the isolation of a closely related cDNA, 2.6 kilobase pairs in length, which we have designated as the FPRL1 receptor cDNA (FPRL1 = formyl peptide receptor like-1). FPR and the FPRL1 receptor derive from small, single-copy genes, both of which are located on human chromosome 19. The gene loci are designated FPR1 and FPRL1, respectively. Both FPR and FPRL1 cDNA cross-hybridize under high stringency conditions with a third gene, designated as FPRL2, which does not appear to be expressed in neutrophils. In contrast, transcripts for both the FPRL1 receptor and FPR are detected only in differentiated myeloid cells; the distribution of N-formyl peptide binding sites is also restricted to mature myeloid cells. FPRL1 cDNA encodes a 351-amino acid polypeptide whose sequence is 69% identical to that of FPR. G protein-coupled receptors that exhibit this degree of structural similarity typically possess a conserved ligand specificity. However, the FPRL1 receptor does not bind prototype N-formyl peptide ligands when expressed in heterologous cell types. 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. Moreover, discovery of the FPRL1 receptor indicates the existence of another as yet unidentified peptide that may recruit neutrophils to sites of inflammation.
Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892.
P M
PM
Murphy
T
T
Ozçelik
R T
RT
Kenney
H L
HL
Tiffany
D
D
McDermott
U
U
Francke
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D002888:Chromosomes, Human, Pair 19; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006822:Hybrid Cells; D008969:Molecular Sequence Data; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000378:metabolism; D009693:Nucleic Acid Hybridization; D010586:Phagocytes / Q000378:metabolism; D012313:RNA / Q000235:genetics; D018075:RNA, Complementary; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism; D044067:Receptors, Lipoxin; D012377:Rodentia; D012689:Sequence Homology, Nucleic Acid; D014158:Transcription, Genetic; D014981:Xenopus
C105101:FPR2 protein, human; D018075:RNA, Complementary; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D044067:Receptors, Lipoxin; D009240:N-Formylmethionine Leucyl-Phenylalanine; D012313:RNA; D004247:DNA; D019204:GTP-Binding Proteins