Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Molecular evolution of the human interleukin–8 receptor gene cluster

Nature Genetics volume 2, pages 31–36 (1992)Cite this article

Abstract

lnterleukin–8 (IL–8) is the prototype for a family of at least eight neutrophil chemoattractants whose genes map to human chromosome 4q13–q21. Two human IL–8 receptors, IL8RA and IL8RB, are known from cDNA cloning; IL8RA is a promiscuous receptor for at least two other related ligands, GROα and NAP–2. We now report cloning of the genes for IL8RA, IL8RB and a recently inactivated pseudogene of receptor A (IL8RAP). These form a cluster of only three genes in the superfamily of G protein–coupled receptors (GPCRs) and map to 2q34–q35. The revolutionary diversity displayed by the IL–8 ligand–receptor complex — ligand promiscuity for IL–8, receptor promiscuity for IL8RA, gene duplication for both ligands and receptors and gene extinction in the case of IL8RAP — is unprecedented for the GPCR superfamily.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Probst, W.C., Snyder, L.A., Schuster, D.I., Brosius, J. & Sealfon, S.C. Sequence alignment of the G-protein coupled receptor superfamily. DNA cell Biol. 11, 1–20 (1992).

    Article  CAS  Google Scholar 

  2. Sen, G.C. & Lengyel, P. The interferon system. A bird's eye view of its biochemistry. J. biol. Chem. 267, 5017–5020 (1992).

    CAS  PubMed  Google Scholar 

  3. Mansukhani, A. et al. Characterization of the murine BEK fibroblast growth factor (FGF) receptor: activation by three members of the FGF family and requirement for heparin. Proc. natn. Acad. Sci. U.S.A. 89, 3305–3309 (1992).

    Article  CAS  Google Scholar 

  4. Sims, J.E. et al. cDNA expression cloning of the IL-1 receptor, a member of the immunoglobulin superfamily. Science 241, 585–589 (1988).

    Article  CAS  Google Scholar 

  5. McMahan, C.J. et al. Anovel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell types. Embo J. 10, 2821–2832 (1991).

    Article  CAS  Google Scholar 

  6. Loetscher, H. et al. Molecular cloning and expression for the human 55kd tumor necrosis factor receptor. Cell 61, 351–359 (1990).

    Article  CAS  Google Scholar 

  7. Smith, C.A. et al. A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. Science 248, 1019–1023 (1990).

    Article  CAS  Google Scholar 

  8. Wolpe, S.D. & Cerami, A. Macrophage inflammatory proteins 1 and 2: members of a novel superfamily of cytokines. FASEB J. 3, 2565–2573 (1989).

    Article  CAS  Google Scholar 

  9. Oppenheim, J.J., Zachariae, C.O.C., Mukaida, N. & Matsushima, K. Properties of the novel proinflammatory supergene “intercrine” cytokine family. Annu. rev. Immunol. 9, 617–648 (1991).

    Article  CAS  Google Scholar 

  10. Baggiolini, M., Walz, A. & Kunkel, S.L. Neutrophil-activating peptide-1/interleukin 8, a novel cytokine that activates neutrophils. J. clin. Invest. 84, 1045–1049 (1989).

    Article  CAS  Google Scholar 

  11. Walz, A. et al. Structure and neutrophil-activating properties of a novel inflammatory peptide (ENA-78) with homology to interleukin 8. J. exp. Med. 174, 1355–1362 (1991).

    Article  CAS  Google Scholar 

  12. Modi, W.S. et al. Monocyte-derived neutrophil chemotactic factor(MDNCF/IL-8) resides in a gene cluster along with several other members of the platelet factor 4 gene superfamily. Hum. Genet. 84, 185–187 (1990).

    Article  CAS  Google Scholar 

  13. Richmond, A. et al. Molecular characterization and chromosomal mapping of melanoma growth stimulatory activity, a growth factor structurally related to β-thromboglobulin. EMBO J. 7, 2025–2033 (1988).

    Article  CAS  Google Scholar 

  14. Griffin, C.A., Emanuel, B.S., LaRocco, P., Schwartz, E. & Poncz, M. Human platelet factor 4 gene is mapped to 4q 12–q21. Cytogenet. Cell Genet. 45, 67–69 (1987).

    Article  CAS  Google Scholar 

  15. Luster, A.D., Jhanwar, S.C., Chaganti, R.S.K., Kersey, J.H. & Ravetch, J.V. Interferon-inducible gene maps to a chromosomal band associated with a (4;11) translocation in acute leukemia cells. Proc. natn. Acad. Sci. U.S.A. 84, 2868–2871 (1987).

    Article  CAS  Google Scholar 

  16. Walz, A., Dewald, B., Tscharner, V., von, M. & Baggiolini, M. Effects of the neutrophil-activating peptide NAP-2, platelet basic protein, connective tissue-activating peptide III, and platelet factor 4 on human neutrophils. J. exp. Med. 170, 1745–1750 (1989).

    Article  CAS  Google Scholar 

  17. Leonard, E.J. et al. Chemotactic activity and receptor binding of neutrophil attractant/activation protein-1 (NAP-1) and structurally related host defense cytokines: interaction of NAP-2 with the NAP-1 receptor. J. leuk. Biol. 49, 258–265 (1991).

    Article  CAS  Google Scholar 

  18. Schnitzel, W., Garbeis, B., Monschein, U. & Besemer, J. Neutrophil activating peptide-2 binds with two affinities to receptor(s) on human neutrophils. Biochem. Biophys. Res. Commun. 180, 301–307 (1991).

    Article  CAS  Google Scholar 

  19. Mukaida, N. et al. Regulation of human interleukin 8 gene expression and binding of several other members of the intercrine family to receptors for interleukin-8. Adv. exp. Med. Biol. 305, 31–38 (1991).

    Article  CAS  Google Scholar 

  20. Murphy, P.M. & Tiffany, H.L. Cloning of complementary DNA encoding a functional human interleukin-8 receptor. Science 253, 1280–1282 (1991).

    Article  CAS  Google Scholar 

  21. Holmes, W.E., Lee, J., Kuang, W.-J., Rice, G.C. & Wood, W.I. Structure and functional expression of a human interleukin-8 receptor. Science 253, 1278–1280 (1991).

    Article  CAS  Google Scholar 

  22. Dohlman, H.G., Thorner, J., Caron, M.G. & Lefkowitz, R.J. Model systems for the study of seven-transmembrane-segment receptors. Annu. Rev. Biochem. 60, 653–688 (1991).

    Article  CAS  Google Scholar 

  23. Strosberg, A.D. Structure/function relationship of proteins belonging to the family of receptors coupled to GTP-binding proteins. Eur. J. Biochem. 196, 1–10 (1991).

    Article  CAS  Google Scholar 

  24. Weishank, R.L. et al. Molecular cloning and characterization of a high affinity dopamine receptor (D1β) and its pseudogene. J. biol. Chem. 266, 22427–22435 (1991).

    Google Scholar 

  25. Grandy, D.K. et al. Multiple human D5 dopamine receptor genes: a functional receptor and two pseudogenes. Proc. natn. Acad. Sci. U.S.A. 88, 9175–9179 (1991).

    Article  CAS  Google Scholar 

  26. Nguyen, T. et al. Human dopamine D5 receptor pseudogenes. Gene 109, 211–218 (1991).

    Article  CAS  Google Scholar 

  27. Yokota, Y. et al. Molecular chacterization of a functional cDNA for rat substance P receptor. J biol. Chem. 264, 17649–17652 (1989).

    CAS  PubMed  Google Scholar 

  28. Fargin, A. et al. The genomic clone G-21 which resembles a β-adrenergic receptor sequence encodes the 5-HT1A receptor. Nature 335, 358–360 (1988).

    Article  CAS  Google Scholar 

  29. Kobilka, B.K. et al. An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins. Nature 329, 75–79 (1987).

    Article  CAS  Google Scholar 

  30. Bao, L., Gerard, N.P., Eddy, R.L., Shows, T.B., Gerard, C. 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, 437–440 (1992).

    Article  CAS  Google Scholar 

  31. Yang-Feng, T.L. et al. Chromosomal organization of adrenergic receptor genes. Proc. natn. Acad. Sci. U.S.A. 87, 1516–1520 (1990).

    Article  CAS  Google Scholar 

  32. Lee, J., Kuang, W-J., Rice, G.C. & Wood, W. I. Characterization of complementary DNA clones encoding the rabbit IL-8 receptor. J. Immunol. 148, 1261–1264 (1992).

    CAS  PubMed  Google Scholar 

  33. Nei, M. & Gojobori, T. Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Molec. biol. Evol. 3, 418–426 (1986).

    CAS  PubMed  Google Scholar 

  34. Li, W.-H., Wu, C.-I. & Luo, C.-C. A new method for estimating synonymous and nonsynonymous rates of nucleotide substitution considering the relative likelihood of nucleotide and codon changes. Molec. biol. Evol. 2, 150–174 (1985).

    PubMed  Google Scholar 

  35. Mattel, M.-G., Pébusque, M.-J. & Birnbaum, D. Chromosomal localizations of mouse Fgf2 and Fgf5 genes. Mamm. Genome 2, 135–137 (1992).

    Article  Google Scholar 

  36. Haskill, S. et al. Identification of three related GRO genes encoding cytokine functions. Proc. natn. Acad. Sci. U.S.A. 87, 7732–7736 (1990).

    Article  CAS  Google Scholar 

  37. Tekamp-Olson, P. et al. Cloning and characterization of cDNAs for murine macrophage inhibitory protein 2 and its human homologues. J. exp. Med. 172, 911–919 (1990).

    Article  CAS  Google Scholar 

  38. Kyte, J. & Doolittle, R.F. A simple method for displaying the hydropathic character of a protein. J. molec. Biol. 157, 105–132 (1982).

    Article  CAS  Google Scholar 

  39. Brooks, J.E. Properties and uses of restriction endonucleases. Methods Enzymol. 152, 113–141, (1987).

    Article  CAS  Google Scholar 

  40. Sanger, F., Nicklen, S. & Coulson, A.R. DNA sequencing with chain-terminating inhibitors. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

    Article  CAS  Google Scholar 

  41. Batzer, M.A. & Deininger, P.L. A human-specific subfamily of Alu sequences. Genomics 9, 481–87 (1991).

    Article  CAS  Google Scholar 

  42. Devereux, J., Haeberli, P. & Smithies, O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 12, 387–395 (1984).

    Article  CAS  Google Scholar 

  43. Francke, U., Yang-Feng, T.L., Brissenden, J.E. & Ullrich, A. Chromosomal mapping of genes involved in growth control. Cold Spring Harbor Symp. quant. Biol. 51, 855–866 (1986).

    Article  CAS  Google Scholar 

  44. Hsieh, C.-L, Vogel, U.S., Dixon, R.A.F. & Francke, U. Chromosomal localization and cDNA sequence of murine and human genes for ras p21 GTPase activating protein (GAP). Somat Cell molec. Genet. 15, 579–590 (1989).

    Article  CAS  Google Scholar 

  45. Milatovich, A., Travis, A., Grosschedl, R. & Francke, U. Gene for lymphoid enhancer-binding factor 1 (LEF1) mapped to human chromosome 4 (q23–q25) and mouse chromosome 3 near Egf. Genomics 11, 1040–1048 (1991).

    Article  CAS  Google Scholar 

  46. Yunis, J.J. High resolution of human chromosomes. Science 191, 1268–1270 (1976).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Sunil K. Ahuja & Philip M. Murphy

  2. Howard Hughes Medical Institute, Stanford, California, 94305-5428, USA

    Tayfun Özçelik & Uta Francke

  3. Department of Genetics, Stanford University Medical Center, Stanford, California, 94305-5428, USA

    Athena Milatovitch & Uta Francke

  4. Department of Pediatrics, Stanford University Medical Center, Stanford, California, 94305-5428, USA

    Uta Francke

Authors
  1. Sunil K. Ahuja
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tayfun Özçelik
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Athena Milatovitch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Uta Francke
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Philip M. Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ahuja, S., Özçelik, T., Milatovitch, A. et al. Molecular evolution of the human interleukin–8 receptor gene cluster. Nat Genet 2, 31–36 (1992). https://doi.org/10.1038/ng0992-31

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ng0992-31

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing