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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
. 1993 Jan 1;90(1):123–127. doi: 10.1073/pnas.90.1.123

Signal transduction mediated by growth hormone receptor and its chimeric molecules with the granulocyte colony-stimulating factor receptor.

E Ishizaka-Ikeda 1, R Fukunaga 1, W I Wood 1, D V Goeddel 1, S Nagata 1
PMCID: PMC45612  PMID: 7678333

Abstract

The granulocyte colony-stimulating factor receptor (G-CSF-R) and growth hormone receptor (GH-R) belong to the cytokine receptor family and have some similarity in the cytokine receptor-homologous (CRH) domain of the extracellular region. Among members of this family, the G-CSF-R and GH-R seem to function as homodimers. Previously, we showed that mouse myeloid precursor FDC-P1 cells expressing the G-CSF-R can respond to G-CSF for growth. Here we show that the GH-R can also transduce the growth signal in FDC-P1 cells in the range 10 pM-100 nM GH. At a higher concentration of GH, GH did not promote the growth of the transformant cells. A series of chimeric receptor cDNAs between the G-CSF-R and GH-R cDNAs was constructed by exon swapping and was expressed in FDC-P1 cells. A ligand-binding assay with transformants expressing chimeric receptors indicated that the entire CRH domain is necessary for specific binding of the ligand. Although the transmembrane and cytoplasmic regions of the G-CSF-R and GH-R have no apparent similarity, these regions were interchangeable, resulting in growth-signal transduction in FDC-P1 cells.

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Selected References

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  1. 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]
  2. Carter-Su C., Stubbart J. R., Wang X. Y., Stred S. E., Argetsinger L. S., Shafer J. A. Phosphorylation of highly purified growth hormone receptors by a growth hormone receptor-associated tyrosine kinase. J Biol Chem. 1989 Nov 5;264(31):18654–18661. [PubMed] [Google Scholar]
  3. Cunningham B. C., Ultsch M., De Vos A. M., Mulkerrin M. G., Clauser K. R., Wells J. A. Dimerization of the extracellular domain of the human growth hormone receptor by a single hormone molecule. Science. 1991 Nov 8;254(5033):821–825. doi: 10.1126/science.1948064. [DOI] [PubMed] [Google Scholar]
  4. Demetri G. D., Griffin J. D. Granulocyte colony-stimulating factor and its receptor. Blood. 1991 Dec 1;78(11):2791–2808. [PubMed] [Google Scholar]
  5. Dexter T. M., Garland J., Scott D., Scolnick E., Metcalf D. Growth of factor-dependent hemopoietic precursor cell lines. J Exp Med. 1980 Oct 1;152(4):1036–1047. doi: 10.1084/jem.152.4.1036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fuh G., Cunningham B. C., Fukunaga R., Nagata S., Goeddel D. V., Wells J. A. Rational design of potent antagonists to the human growth hormone receptor. Science. 1992 Jun 19;256(5064):1677–1680. doi: 10.1126/science.256.5064.1677. [DOI] [PubMed] [Google Scholar]
  7. Fuh G., Mulkerrin M. G., Bass S., McFarland N., Brochier M., Bourell J. H., Light D. R., Wells J. A. The human growth hormone receptor. Secretion from Escherichia coli and disulfide bonding pattern of the extracellular binding domain. J Biol Chem. 1990 Feb 25;265(6):3111–3115. [PubMed] [Google Scholar]
  8. Fukunaga R., Ishizaka-Ikeda E., Nagata S. Purification and characterization of the receptor for murine granulocyte colony-stimulating factor. J Biol Chem. 1990 Aug 15;265(23):14008–14015. [PubMed] [Google Scholar]
  9. Fukunaga R., Ishizaka-Ikeda E., Pan C. X., Seto Y., Nagata S. Functional domains of the granulocyte colony-stimulating factor receptor. EMBO J. 1991 Oct;10(10):2855–2865. doi: 10.1002/j.1460-2075.1991.tb07835.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fukunaga R., Ishizaka-Ikeda E., Seto Y., Nagata S. Expression cloning of a receptor for murine granulocyte colony-stimulating factor. Cell. 1990 Apr 20;61(2):341–350. doi: 10.1016/0092-8674(90)90814-u. [DOI] [PubMed] [Google Scholar]
  11. Fukunaga R., Seto Y., Mizushima S., Nagata S. Three different mRNAs encoding human granulocyte colony-stimulating factor receptor. Proc Natl Acad Sci U S A. 1990 Nov;87(22):8702–8706. doi: 10.1073/pnas.87.22.8702. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Godowski P. J., Leung D. W., Meacham L. R., Galgani J. P., Hellmiss R., Keret R., Rotwein P. S., Parks J. S., Laron Z., Wood W. I. Characterization of the human growth hormone receptor gene and demonstration of a partial gene deletion in two patients with Laron-type dwarfism. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8083–8087. doi: 10.1073/pnas.86.20.8083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hughes J. P., Friesen H. G. The nature and regulation of the receptors for pituitary growth hormone. Annu Rev Physiol. 1985;47:469–482. doi: 10.1146/annurev.ph.47.030185.002345. [DOI] [PubMed] [Google Scholar]
  14. Isaksson O. G., Edén S., Jansson J. O. Mode of action of pituitary growth hormone on target cells. Annu Rev Physiol. 1985;47:483–499. doi: 10.1146/annurev.ph.47.030185.002411. [DOI] [PubMed] [Google Scholar]
  15. Kaushansky K., Shoemaker S. G., Alfaro S., Brown C. Hematopoietic activity of granulocyte/macrophage colony-stimulating factor is dependent upon two distinct regions of the molecule: functional analysis based upon the activities of interspecies hybrid growth factors. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1213–1217. doi: 10.1073/pnas.86.4.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Leung D. W., Spencer S. A., Cachianes G., Hammonds R. G., Collins C., Henzel W. J., Barnard R., Waters M. J., Wood W. I. Growth hormone receptor and serum binding protein: purification, cloning and expression. Nature. 1987 Dec 10;330(6148):537–543. doi: 10.1038/330537a0. [DOI] [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. Nagata S., Fukunaga R. Granulocyte colony-stimulating factor and its receptor. Prog Growth Factor Res. 1991;3(2):131–141. doi: 10.1016/s0955-2235(05)80004-3. [DOI] [PubMed] [Google Scholar]
  19. Nicola N. A. Hemopoietic cell growth factors and their receptors. Annu Rev Biochem. 1989;58:45–77. doi: 10.1146/annurev.bi.58.070189.000401. [DOI] [PubMed] [Google Scholar]
  20. Nicoll C. S., Mayer G. L., Russell S. M. Structural features of prolactins and growth hormones that can be related to their biological properties. Endocr Rev. 1986 May;7(2):169–203. doi: 10.1210/edrv-7-2-169. [DOI] [PubMed] [Google Scholar]
  21. Roussel M. F., Transy C., Kato J. Y., Reinherz E. L., Sherr C. J. Antibody-induced mitogenicity mediated by a chimeric CD2-c-fms receptor. Mol Cell Biol. 1990 May;10(5):2407–2412. doi: 10.1128/mcb.10.5.2407. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schreurs J., Hung P., May W. S., Arai K., Miyajima A. AIC2A is a component of the purified high affinity mouse IL-3 receptor: temperature-dependent modulation of AIC2A structure. Int Immunol. 1991 Dec;3(12):1231–1242. doi: 10.1093/intimm/3.12.1231. [DOI] [PubMed] [Google Scholar]
  23. Seto Y., Fukunaga R., Nagata S. Chromosomal gene organization of the human granulocyte colony-stimulating factor receptor. J Immunol. 1992 Jan 1;148(1):259–266. [PubMed] [Google Scholar]
  24. Streuli M., Hall A., Boll W., Stewart W. E., 2nd, Nagata S., Weissmann C. Target cell specificity of two species of human interferon-alpha produced in Escherichia coli and of hybrid molecules derived from them. Proc Natl Acad Sci U S A. 1981 May;78(5):2848–2852. doi: 10.1073/pnas.78.5.2848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Weck P. K., Apperson S., Stebbing N., Gray P. W., Leung D., Shepard H. M., Goeddel D. V. Antiviral activities of hybrids of two major human leukocyte interferons. Nucleic Acids Res. 1981 Nov 25;9(22):6153–6166. doi: 10.1093/nar/9.22.6153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. de Vos A. M., Ultsch M., Kossiakoff A. A. Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science. 1992 Jan 17;255(5042):306–312. doi: 10.1126/science.1549776. [DOI] [PubMed] [Google Scholar]

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