Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1996 Jan 9;93(1):497–501. doi: 10.1073/pnas.93.1.497

Cloning and characterization of a binding subunit of the interleukin 13 receptor that is also a component of the interleukin 4 receptor.

D J Hilton 1, J G Zhang 1, D Metcalf 1, W S Alexander 1, N A Nicola 1, T A Willson 1
PMCID: PMC40265  PMID: 8552669

Abstract

Interleukins 4 (IL-4) and 13 (IL-13) have been found previously to share receptor components on some cells, as revealed by receptor cross-competition studies. In the present study, the cloning is described of murine NR4, a previously unrecognized receptor identified on the basis of sequence similarity with members of the hemopoietin receptor family. mRNA encoding NR4 was found in a wide range of murine cells and tissues. By using transient expression in COS-7 cells, NR4 was found to encode the IL-13 receptor alpha chain, a low-affinity receptor capable of binding IL-13 but not IL-4 or interleukins 2, -7, -9, or -15. Stable expression of the IL-13 receptor alpha chain (NR4) in CTLL-2 cells resulted in the generation of high-affinity IL-13 receptors capable of transducing a proliferative signal in response to IL-13 and, moreover, led to competitive cross-reactivity in the binding of IL-4 and IL-13. These results suggest that the IL-13 receptor alpha chain (NR4) is the primary binding subunit of the IL-13 receptor and may also be a component of IL-4 receptors.

Full text

PDF
497

Images in this article

499Fig. 2
on p.499

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aversa G., Punnonen J., Cocks B. G., de Waal Malefyt R., Vega F., Jr, Zurawski S. M., Zurawski G., de Vries J. E. An interleukin 4 (IL-4) mutant protein inhibits both IL-4 or IL-13-induced human immunoglobulin G4 (IgG4) and IgE synthesis and B cell proliferation: support for a common component shared by IL-4 and IL-13 receptors. J Exp Med. 1993 Dec 1;178(6):2213–2218. doi: 10.1084/jem.178.6.2213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Contreras M. A., Bale W. F., Spar I. L. Iodine monochloride (IC1) iodination techniques. Methods Enzymol. 1983;92:277–292. [PubMed] [Google Scholar]
  3. Davis I. D., Treutlein H. R., Friedrich K., Burgess A. W. A potent human interleukin-4 antagonist stimulates the proliferation of murine cells expressing the human interleukin-4 binding chain. Growth Factors. 1995;12(1):69–83. doi: 10.3109/08977199509003215. [DOI] [PubMed] [Google Scholar]
  4. Dugaiczyk A., Haron J. A., Stone E. M., Dennison O. E., Rothblum K. N., Schwartz R. J. Cloning and sequencing of a deoxyribonucleic acid copy of glyceraldehyde-3-phosphate dehydrogenase messenger ribonucleic acid isolated from chicken muscle. Biochemistry. 1983 Mar 29;22(7):1605–1613. doi: 10.1021/bi00276a013. [DOI] [PubMed] [Google Scholar]
  5. Gearing D. P., Bruce A. G. Oncostatin M binds the high-affinity leukemia inhibitory factor receptor. New Biol. 1992 Jan;4(1):61–65. [PubMed] [Google Scholar]
  6. Gearing D. P., Comeau M. R., Friend D. J., Gimpel S. D., Thut C. J., McGourty J., Brasher K. K., King J. A., Gillis S., Mosley B. The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the LIF receptor. Science. 1992 Mar 13;255(5050):1434–1437. doi: 10.1126/science.1542794. [DOI] [PubMed] [Google Scholar]
  7. Giri J. G., Ahdieh M., Eisenman J., Shanebeck K., Grabstein K., Kumaki S., Namen A., Park L. S., Cosman D., Anderson D. Utilization of the beta and gamma chains of the IL-2 receptor by the novel cytokine IL-15. EMBO J. 1994 Jun 15;13(12):2822–2830. doi: 10.1002/j.1460-2075.1994.tb06576.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. He Y. W., Adkins B., Furse R. K., Malek T. R. Expression and function of the gamma c subunit of the IL-2, IL-4, and IL-7 receptors. Distinct interaction of gamma c in the IL-4 receptor. J Immunol. 1995 Feb 15;154(4):1596–1605. [PubMed] [Google Scholar]
  9. Hilton D. J., Hilton A. A., Raicevic A., Rakar S., Harrison-Smith M., Gough N. M., Begley C. G., Metcalf D., Nicola N. A., Willson T. A. Cloning of a murine IL-11 receptor alpha-chain; requirement for gp130 for high affinity binding and signal transduction. EMBO J. 1994 Oct 17;13(20):4765–4775. doi: 10.1002/j.1460-2075.1994.tb06802.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hilton D. J., Nicola N. A. Kinetic analyses of the binding of leukemia inhibitory factor to receptor on cells and membranes and in detergent solution. J Biol Chem. 1992 May 25;267(15):10238–10247. [PubMed] [Google Scholar]
  11. Kimura Y., Takeshita T., Kondo M., Ishii N., Nakamura M., Van Snick J., Sugamura K. Sharing of the IL-2 receptor gamma chain with the functional IL-9 receptor complex. Int Immunol. 1995 Jan;7(1):115–120. doi: 10.1093/intimm/7.1.115. [DOI] [PubMed] [Google Scholar]
  12. Kondo M., Takeshita T., Higuchi M., Nakamura M., Sudo T., Nishikawa S., Sugamura K. Functional participation of the IL-2 receptor gamma chain in IL-7 receptor complexes. Science. 1994 Mar 11;263(5152):1453–1454. doi: 10.1126/science.8128231. [DOI] [PubMed] [Google Scholar]
  13. Kondo M., Takeshita T., Ishii N., Nakamura M., Watanabe S., Arai K., Sugamura K. Sharing of the interleukin-2 (IL-2) receptor gamma chain between receptors for IL-2 and IL-4. Science. 1993 Dec 17;262(5141):1874–1877. doi: 10.1126/science.8266076. [DOI] [PubMed] [Google Scholar]
  14. Lin J. X., Migone T. S., Tsang M., Friedmann M., Weatherbee J. A., Zhou L., Yamauchi A., Bloom E. T., Mietz J., John S. The role of shared receptor motifs and common Stat proteins in the generation of cytokine pleiotropy and redundancy by IL-2, IL-4, IL-7, IL-13, and IL-15. Immunity. 1995 Apr;2(4):331–339. doi: 10.1016/1074-7613(95)90141-8. [DOI] [PubMed] [Google Scholar]
  15. Lock P., Metcalf D., Nicola N. A. Histidine-367 of the human common beta chain of the receptor is critical for high-affinity binding of human granulocyte-macrophage colony-stimulating factor. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):252–256. doi: 10.1073/pnas.91.1.252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Matthews D. J., Clark P. A., Herbert J., Morgan G., Armitage R. J., Kinnon C., Minty A., Grabstein K. H., Caput D., Ferrara P. Function of the interleukin-2 (IL-2) receptor gamma-chain in biologic responses of X-linked severe combined immunodeficient B cells to IL-2, IL-4, IL-13, and IL-15. Blood. 1995 Jan 1;85(1):38–42. [PubMed] [Google Scholar]
  17. Mizushima S., Nagata S. pEF-BOS, a powerful mammalian expression vector. Nucleic Acids Res. 1990 Sep 11;18(17):5322–5322. doi: 10.1093/nar/18.17.5322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mosley B., Beckmann M. P., March C. J., Idzerda R. L., Gimpel S. D., VandenBos T., Friend D., Alpert A., Anderson D., Jackson J. The murine interleukin-4 receptor: molecular cloning and characterization of secreted and membrane bound forms. Cell. 1989 Oct 20;59(2):335–348. doi: 10.1016/0092-8674(89)90295-x. [DOI] [PubMed] [Google Scholar]
  19. Noguchi M., Nakamura Y., Russell S. M., Ziegler S. F., Tsang M., Cao X., Leonard W. J. Interleukin-2 receptor gamma chain: a functional component of the interleukin-7 receptor. Science. 1993 Dec 17;262(5141):1877–1880. doi: 10.1126/science.8266077. [DOI] [PubMed] [Google Scholar]
  20. Obiri N. I., Debinski W., Leonard W. J., Puri R. K. Receptor for interleukin 13. Interaction with interleukin 4 by a mechanism that does not involve the common gamma chain shared by receptors for interleukins 2, 4, 7, 9, and 15. J Biol Chem. 1995 Apr 14;270(15):8797–8804. doi: 10.1074/jbc.270.15.8797. [DOI] [PubMed] [Google Scholar]
  21. Russell S. M., Keegan A. D., Harada N., Nakamura Y., Noguchi M., Leland P., Friedmann M. C., Miyajima A., Puri R. K., Paul W. E. Interleukin-2 receptor gamma chain: a functional component of the interleukin-4 receptor. Science. 1993 Dec 17;262(5141):1880–1883. doi: 10.1126/science.8266078. [DOI] [PubMed] [Google Scholar]
  22. Smerz-Bertling C., Duschl A. Both interleukin 4 and interleukin 13 induce tyrosine phosphorylation of the 140-kDa subunit of the interleukin 4 receptor. J Biol Chem. 1995 Jan 13;270(2):966–970. doi: 10.1074/jbc.270.2.966. [DOI] [PubMed] [Google Scholar]
  23. Takeshita T., Asao H., Ohtani K., Ishii N., Kumaki S., Tanaka N., Munakata H., Nakamura M., Sugamura K. Cloning of the gamma chain of the human IL-2 receptor. Science. 1992 Jul 17;257(5068):379–382. doi: 10.1126/science.1631559. [DOI] [PubMed] [Google Scholar]
  24. Thoma B., Bird T. A., Friend D. J., Gearing D. P., Dower S. K. Oncostatin M and leukemia inhibitory factor trigger overlapping and different signals through partially shared receptor complexes. J Biol Chem. 1994 Feb 25;269(8):6215–6222. [PubMed] [Google Scholar]
  25. Tony H. P., Shen B. J., Reusch P., Sebald W. Design of human interleukin-4 antagonists inhibiting interleukin-4-dependent and interleukin-13-dependent responses in T-cells and B-cells with high efficiency. Eur J Biochem. 1994 Oct 15;225(2):659–665. doi: 10.1111/j.1432-1033.1994.00659.x. [DOI] [PubMed] [Google Scholar]
  26. Vita N., Lefort S., Laurent P., Caput D., Ferrara P. Characterization and comparison of the interleukin 13 receptor with the interleukin 4 receptor on several cell types. J Biol Chem. 1995 Feb 24;270(8):3512–3517. doi: 10.1074/jbc.270.8.3512. [DOI] [PubMed] [Google Scholar]
  27. Zurawski G., de Vries J. E. Interleukin 13, an interleukin 4-like cytokine that acts on monocytes and B cells, but not on T cells. Immunol Today. 1994 Jan;15(1):19–26. doi: 10.1016/0167-5699(94)90021-3. [DOI] [PubMed] [Google Scholar]
  28. Zurawski S. M., Chomarat P., Djossou O., Bidaud C., McKenzie A. N., Miossec P., Banchereau J., Zurawski G. The primary binding subunit of the human interleukin-4 receptor is also a component of the interleukin-13 receptor. J Biol Chem. 1995 Jun 9;270(23):13869–13878. doi: 10.1074/jbc.270.23.13869. [DOI] [PubMed] [Google Scholar]
  29. Zurawski S. M., Vega F., Jr, Huyghe B., Zurawski G. Receptors for interleukin-13 and interleukin-4 are complex and share a novel component that functions in signal transduction. EMBO J. 1993 Jul;12(7):2663–2670. doi: 10.1002/j.1460-2075.1993.tb05927.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES