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. 1994 Oct 17;13(20):4765–4775. doi: 10.1002/j.1460-2075.1994.tb06802.x

Cloning of a murine IL-11 receptor alpha-chain; requirement for gp130 for high affinity binding and signal transduction.

D J Hilton 1, A A Hilton 1, A Raicevic 1, S Rakar 1, M Harrison-Smith 1, N M Gough 1, C G Begley 1, D Metcalf 1, N A Nicola 1, T A Willson 1
PMCID: PMC395415  PMID: 7957045

Abstract

An adult mouse liver cDNA library was screened with oligonucleotides corresponding to the conserved WSXWS motif of the haemopoietin receptor family. Using this method, cDNA clones encoding a novel receptor were isolated. The new receptor, named NR1, was most similar in sequence and predicted structure to the alpha-chain of the IL-6 receptor and mRNA was expressed in the 3T3-L1 pre-adipocytic cell line and in a range of primary tissues. Expression of NR1 in the factor-dependent haemopoietic cell line Ba/F3 resulted in the generation of low affinity receptors for IL-11 (Kd approximately 10 nM). The capacity to bind IL-11 with high affinity (Kd = 300-800 pM) appeared to require coexpression of both NR1 and gp130, the common subunit of the IL-6, leukaemia inhibitory factor (LIF), oncostatin M (OSM) and ciliary neurotrophic factor (CNTF) receptors. The expression of both NR1 and gp130 was also necessary for Ba/F3 cells to proliferate and M1 cells to undergo macrophage differentiation in response to IL-11.

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Selected References

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

  1. Armitage R. J., Fanslow W. C., Strockbine L., Sato T. A., Clifford K. N., Macduff B. M., Anderson D. M., Gimpel S. D., Davis-Smith T., Maliszewski C. R. Molecular and biological characterization of a murine ligand for CD40. Nature. 1992 May 7;357(6373):80–82. doi: 10.1038/357080a0. [DOI] [PubMed] [Google Scholar]
  2. Baumann H., Schendel P. Interleukin-11 regulates the hepatic expression of the same plasma protein genes as interleukin-6. J Biol Chem. 1991 Oct 25;266(30):20424–20427. [PubMed] [Google Scholar]
  3. Bazan J. F. Structural design and molecular evolution of a cytokine receptor superfamily. Proc Natl Acad Sci U S A. 1990 Sep;87(18):6934–6938. doi: 10.1073/pnas.87.18.6934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bolton A. E., Hunter W. M. The labelling of proteins to high specific radioactivities by conjugation to a 125I-containing acylating agent. Biochem J. 1973 Jul;133(3):529–539. doi: 10.1042/bj1330529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Buck L., Axel R. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell. 1991 Apr 5;65(1):175–187. doi: 10.1016/0092-8674(91)90418-x. [DOI] [PubMed] [Google Scholar]
  6. Burstein S. A., Mei R. L., Henthorn J., Friese P., Turner K. Leukemia inhibitory factor and interleukin-11 promote maturation of murine and human megakaryocytes in vitro. J Cell Physiol. 1992 Nov;153(2):305–312. doi: 10.1002/jcp.1041530210. [DOI] [PubMed] [Google Scholar]
  7. Calvo J. C., Radicella J. P., Charreau E. H. Measurement of specific radioactivities in labelled hormones by self-displacement analysis. Biochem J. 1983 May 15;212(2):259–264. doi: 10.1042/bj2120259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Camerini D., Walz G., Loenen W. A., Borst J., Seed B. The T cell activation antigen CD27 is a member of the nerve growth factor/tumor necrosis factor receptor gene family. J Immunol. 1991 Nov 1;147(9):3165–3169. [PubMed] [Google Scholar]
  9. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  10. Cosman D., Lyman S. D., Idzerda R. L., Beckmann M. P., Park L. S., Goodwin R. G., March C. J. A new cytokine receptor superfamily. Trends Biochem Sci. 1990 Jul;15(7):265–270. doi: 10.1016/0968-0004(90)90051-c. [DOI] [PubMed] [Google Scholar]
  11. Davis S., Aldrich T. H., Stahl N., Pan L., Taga T., Kishimoto T., Ip N. Y., Yancopoulos G. D. LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor. Science. 1993 Jun 18;260(5115):1805–1808. doi: 10.1126/science.8390097. [DOI] [PubMed] [Google Scholar]
  12. Davis S., Aldrich T. H., Valenzuela D. M., Wong V. V., Furth M. E., Squinto S. P., Yancopoulos G. D. The receptor for ciliary neurotrophic factor. Science. 1991 Jul 5;253(5015):59–63. doi: 10.1126/science.1648265. [DOI] [PubMed] [Google Scholar]
  13. Davis S., Yancopoulos G. D. The molecular biology of the CNTF receptor. Curr Opin Neurobiol. 1993 Feb;3(1):20–24. doi: 10.1016/0959-4388(93)90030-3. [DOI] [PubMed] [Google Scholar]
  14. Du X. X., Williams D. A. Interleukin-11: a multifunctional growth factor derived from the hematopoietic microenvironment. Blood. 1994 Apr 15;83(8):2023–2030. [PubMed] [Google Scholar]
  15. Fann M. J., Patterson P. H. Neuropoietic cytokines and activin A differentially regulate the phenotype of cultured sympathetic neurons. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):43–47. doi: 10.1073/pnas.91.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. Gearing D. P., King J. A., Gough N. M., Nicola N. A. Expression cloning of a receptor for human granulocyte-macrophage colony-stimulating factor. EMBO J. 1989 Dec 1;8(12):3667–3676. doi: 10.1002/j.1460-2075.1989.tb08541.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Gearing D. P., Thut C. J., VandeBos T., Gimpel S. D., Delaney P. B., King J., Price V., Cosman D., Beckmann M. P. Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130. EMBO J. 1991 Oct;10(10):2839–2848. doi: 10.1002/j.1460-2075.1991.tb07833.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Gonda T. J., Sheiness D. K., Bishop J. M. Transcripts from the cellular homologs of retroviral oncogenes: distribution among chicken tissues. Mol Cell Biol. 1982 Jun;2(6):617–624. doi: 10.1128/mcb.2.6.617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Goodwin R. G., Alderson M. R., Smith C. A., Armitage R. J., VandenBos T., Jerzy R., Tough T. W., Schoenborn M. A., Davis-Smith T., Hennen K. Molecular and biological characterization of a ligand for CD27 defines a new family of cytokines with homology to tumor necrosis factor. Cell. 1993 May 7;73(3):447–456. doi: 10.1016/0092-8674(93)90133-b. [DOI] [PubMed] [Google Scholar]
  22. Gough N. M. Rapid and quantitative preparation of cytoplasmic RNA from small numbers of cells. Anal Biochem. 1988 Aug 15;173(1):93–95. doi: 10.1016/0003-2697(88)90164-9. [DOI] [PubMed] [Google Scholar]
  23. Hangoc G., Yin T., Cooper S., Schendel P., Yang Y. C., Broxmeyer H. E. In vivo effects of recombinant interleukin-11 on myelopoiesis in mice. Blood. 1993 Feb 15;81(4):965–972. [PubMed] [Google Scholar]
  24. Hibi M., Murakami M., Saito M., Hirano T., Taga T., Kishimoto T. Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell. 1990 Dec 21;63(6):1149–1157. doi: 10.1016/0092-8674(90)90411-7. [DOI] [PubMed] [Google Scholar]
  25. Hilton D. J. LIF: lots of interesting functions. Trends Biochem Sci. 1992 Feb;17(2):72–76. doi: 10.1016/0968-0004(92)90505-4. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Hilton D. J., Nicola N. A., Metcalf D. Specific binding of murine leukemia inhibitory factor to normal and leukemic monocytic cells. Proc Natl Acad Sci U S A. 1988 Aug;85(16):5971–5975. doi: 10.1073/pnas.85.16.5971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ichikawa Y. Differentiation of a cell line of myeloid leukemia. J Cell Physiol. 1969 Dec;74(3):223–234. doi: 10.1002/jcp.1040740303. [DOI] [PubMed] [Google Scholar]
  29. Ip N. Y., Nye S. H., Boulton T. G., Davis S., Taga T., Li Y., Birren S. J., Yasukawa K., Kishimoto T., Anderson D. J. CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130. Cell. 1992 Jun 26;69(7):1121–1132. doi: 10.1016/0092-8674(92)90634-o. [DOI] [PubMed] [Google Scholar]
  30. Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M., Hase A., Seto Y., Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233–243. doi: 10.1016/0092-8674(91)90614-5. [DOI] [PubMed] [Google Scholar]
  31. Kawashima I., Ohsumi J., Mita-Honjo K., Shimoda-Takano K., Ishikawa H., Sakakibara S., Miyadai K., Takiguchi Y. Molecular cloning of cDNA encoding adipogenesis inhibitory factor and identity with interleukin-11. FEBS Lett. 1991 Jun 3;283(2):199–202. doi: 10.1016/0014-5793(91)80587-s. [DOI] [PubMed] [Google Scholar]
  32. Keller D. C., Du X. X., Srour E. F., Hoffman R., Williams D. A. Interleukin-11 inhibits adipogenesis and stimulates myelopoiesis in human long-term marrow cultures. Blood. 1993 Sep 1;82(5):1428–1435. [PubMed] [Google Scholar]
  33. Kishimoto T., Akira S., Taga T. Interleukin-6 and its receptor: a paradigm for cytokines. Science. 1992 Oct 23;258(5082):593–597. doi: 10.1126/science.1411569. [DOI] [PubMed] [Google Scholar]
  34. Kishimoto T., Taga T., Akira S. Cytokine signal transduction. Cell. 1994 Jan 28;76(2):253–262. doi: 10.1016/0092-8674(94)90333-6. [DOI] [PubMed] [Google Scholar]
  35. Lyman S. D., James L., Vanden Bos T., de Vries P., Brasel K., Gliniak B., Hollingsworth L. T., Picha K. S., McKenna H. J., Splett R. R. Molecular cloning of a ligand for the flt3/flk-2 tyrosine kinase receptor: a proliferative factor for primitive hematopoietic cells. Cell. 1993 Dec 17;75(6):1157–1167. doi: 10.1016/0092-8674(93)90325-k. [DOI] [PubMed] [Google Scholar]
  36. Miyajima A., Hara T., Kitamura T. Common subunits of cytokine receptors and the functional redundancy of cytokines. Trends Biochem Sci. 1992 Oct;17(10):378–382. doi: 10.1016/0968-0004(92)90004-s. [DOI] [PubMed] [Google Scholar]
  37. Miyajima A. Molecular structure of the IL-3, GM-CSF and IL-5 receptors. Int J Cell Cloning. 1992 May;10(3):126–134. doi: 10.1002/stem.5530100302. [DOI] [PubMed] [Google Scholar]
  38. 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]
  39. Murakami M., Hibi M., Nakagawa N., Nakagawa T., Yasukawa K., Yamanishi K., Taga T., Kishimoto T. IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase. Science. 1993 Jun 18;260(5115):1808–1810. doi: 10.1126/science.8511589. [DOI] [PubMed] [Google Scholar]
  40. Musashi M., Clark S. C., Sudo T., Urdal D. L., Ogawa M. Synergistic interactions between interleukin-11 and interleukin-4 in support of proliferation of primitive hematopoietic progenitors of mice. Blood. 1991 Sep 15;78(6):1448–1451. [PubMed] [Google Scholar]
  41. Nicola N. A., Metcalf D. Subunit promiscuity among hemopoietic growth factor receptors. Cell. 1991 Oct 4;67(1):1–4. doi: 10.1016/0092-8674(91)90564-f. [DOI] [PubMed] [Google Scholar]
  42. Palacios R., Steinmetz M. Il-3-dependent mouse clones that express B-220 surface antigen, contain Ig genes in germ-line configuration, and generate B lymphocytes in vivo. Cell. 1985 Jul;41(3):727–734. doi: 10.1016/s0092-8674(85)80053-2. [DOI] [PubMed] [Google Scholar]
  43. Paul S. R., Bennett F., Calvetti J. A., Kelleher K., Wood C. R., O'Hara R. M., Jr, Leary A. C., Sibley B., Clark S. C., Williams D. A. Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7512–7516. doi: 10.1073/pnas.87.19.7512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Peles E., Bacus S. S., Koski R. A., Lu H. S., Wen D., Ogden S. G., Levy R. B., Yarden Y. Isolation of the neu/HER-2 stimulatory ligand: a 44 kd glycoprotein that induces differentiation of mammary tumor cells. Cell. 1992 Apr 3;69(1):205–216. doi: 10.1016/0092-8674(92)90131-u. [DOI] [PubMed] [Google Scholar]
  45. Reed K. C., Mann D. A. Rapid transfer of DNA from agarose gels to nylon membranes. Nucleic Acids Res. 1985 Oct 25;13(20):7207–7221. doi: 10.1093/nar/13.20.7207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Rose T. M., Bruce A. G. Oncostatin M is a member of a cytokine family that includes leukemia-inhibitory factor, granulocyte colony-stimulating factor, and interleukin 6. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8641–8645. doi: 10.1073/pnas.88.19.8641. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Schibler K. R., Yang Y. C., Christensen R. D. Effect of interleukin-11 on cycling status and clonogenic maturation of fetal and adult hematopoietic progenitors. Blood. 1992 Aug 15;80(4):900–903. [PubMed] [Google Scholar]
  49. Suda T., Takahashi T., Golstein P., Nagata S. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell. 1993 Dec 17;75(6):1169–1178. doi: 10.1016/0092-8674(93)90326-l. [DOI] [PubMed] [Google Scholar]
  50. Teramura M., Kobayashi S., Hoshino S., Oshimi K., Mizoguchi H. Interleukin-11 enhances human megakaryocytopoiesis in vitro. Blood. 1992 Jan 15;79(2):327–331. [PubMed] [Google Scholar]
  51. Tsuji K., Lyman S. D., Sudo T., Clark S. C., Ogawa M. Enhancement of murine hematopoiesis by synergistic interactions between steel factor (ligand for c-kit), interleukin-11, and other early acting factors in culture. Blood. 1992 Jun 1;79(11):2855–2860. [PubMed] [Google Scholar]
  52. Yamasaki K., Taga T., Hirata Y., Yawata H., Kawanishi Y., Seed B., Taniguchi T., Hirano T., Kishimoto T. Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor. Science. 1988 Aug 12;241(4867):825–828. doi: 10.1126/science.3136546. [DOI] [PubMed] [Google Scholar]
  53. Yang Y. C., Yin T. Interleukin-11 and its receptor. Biofactors. 1992 Dec;4(1):15–21. [PubMed] [Google Scholar]
  54. Yin T., Miyazawa K., Yang Y. C. Characterization of interleukin-11 receptor and protein tyrosine phosphorylation induced by interleukin-11 in mouse 3T3-L1 cells. J Biol Chem. 1992 Apr 25;267(12):8347–8351. [PubMed] [Google Scholar]
  55. Yin T., Taga T., Tsang M. L., Yasukawa K., Kishimoto T., Yang Y. C. Involvement of IL-6 signal transducer gp130 in IL-11-mediated signal transduction. J Immunol. 1993 Sep 1;151(5):2555–2561. [PubMed] [Google Scholar]
  56. Yonemura Y., Kawakita M., Masuda T., Fujimoto K., Kato K., Takatsuki K. Synergistic effects of interleukin 3 and interleukin 11 on murine megakaryopoiesis in serum-free culture. Exp Hematol. 1992 Sep;20(8):1011–1016. [PubMed] [Google Scholar]

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