Abstract
The granulocyte/macrophage colony-stimulating factor (GM-CSF) receptor (GMR) transduces a signal that results in the proliferation, differentiation, and functional activation of hematopoietic cells. This study sought to determine whether functional isoforms of the receptor exist that may be important in generating this diversity of cellular response. We have isolated a cDNA encoding an isoform of the low-affinity human GMR that is a product of alternative splicing of the GMR gene and results in a predicted 410-amino acid protein with a cytoplasmic domain that is rich in serine residues, a feature of regions critical in signal transduction for other receptors of the hematopoietin receptor superfamily. This receptor bound ligand and was functionally active when introduced into a murine factor-dependent cell line; mRNA transcripts representative of this isoform were coexpressed with those for a previously isolated 400-amino acid isoform of the GMR in normal hematopoietic and leukemic cells. In view of the recent isolation of a cDNA, designated GM-CSF R beta, that confers high-affinity binding of GM-CSF in cotransfection experiments with the low-affinity receptor, we suggest that the previously isolated low-affinity receptor be designated GM-CSF R alpha 1 and the one described in this report be designated GM-CSF R alpha 2.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ashworth A., Kraft A. Cloning of a potentially soluble receptor for human GM-CSF. Nucleic Acids Res. 1990 Dec 11;18(23):7178–7178. doi: 10.1093/nar/18.23.7178. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Avanzi G. C., Lista P., Giovinazzo B., Miniero R., Saglio G., Benetton G., Coda R., Cattoretti G., Pegoraro L. Selective growth response to IL-3 of a human leukaemic cell line with megakaryoblastic features. Br J Haematol. 1988 Jul;69(3):359–366. doi: 10.1111/j.1365-2141.1988.tb02374.x. [DOI] [PubMed] [Google Scholar]
- Budel L. M., Elbaz O., Hoogerbrugge H., Delwel R., Mahmoud L. A., Löwenberg B., Touw I. P. Common binding structure for granulocyte macrophage colony-stimulating factor and interleukin-3 on human acute myeloid leukemia cells and monocytes. Blood. 1990 Apr 1;75(7):1439–1445. [PubMed] [Google Scholar]
- Cannistra S. A., Koenigsmann M., DiCarlo J., Groshek P., Griffin J. D. Differentiation-associated expression of two functionally distinct classes of granulocyte-macrophage colony-stimulating factor receptors by human myeloid cells. J Biol Chem. 1990 Jul 25;265(21):12656–12663. [PubMed] [Google Scholar]
- Chiba S., Tojo A., Kitamura T., Urabe A., Miyazono K., Takaku F. Characterization and molecular features of the cell surface receptor for human granulocyte-macrophage colony-stimulating factor. Leukemia. 1990 Jan;4(1):29–36. [PubMed] [Google Scholar]
- Contreras M. A., Bale W. F., Spar I. L. Iodine monochloride (IC1) iodination techniques. Methods Enzymol. 1983;92:277–292. [PubMed] [Google Scholar]
- D'Andrea A. D., Fasman G. D., Lodish H. F. Erythropoietin receptor and interleukin-2 receptor beta chain: a new receptor family. Cell. 1989 Sep 22;58(6):1023–1024. doi: 10.1016/0092-8674(89)90499-6. [DOI] [PubMed] [Google Scholar]
- D'Andrea A. D., Yoshimura A., Youssoufian H., Zon L. I., Koo J. W., Lodish H. F. The cytoplasmic region of the erythropoietin receptor contains nonoverlapping positive and negative growth-regulatory domains. Mol Cell Biol. 1991 Apr;11(4):1980–1987. doi: 10.1128/mcb.11.4.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Donahue R. E., Wang E. A., Stone D. K., Kamen R., Wong G. G., Sehgal P. K., Nathan D. G., Clark S. C. Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF. 1986 Jun 26-Jul 2Nature. 321(6073):872–875. doi: 10.1038/321872a0. [DOI] [PubMed] [Google Scholar]
- Elliott M. J., Vadas M. A., Eglinton J. M., Park L. S., To L. B., Cleland L. G., Clark S. C., Lopez A. F. Recombinant human interleukin-3 and granulocyte-macrophage colony-stimulating factor show common biological effects and binding characteristics on human monocytes. Blood. 1989 Nov 15;74(7):2349–2359. [PubMed] [Google Scholar]
- 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]
- Gasson J. C., Kaufman S. E., Weisbart R. H., Tomonaga M., Golde D. W. High-affinity binding of granulocyte-macrophage colony-stimulating factor to normal and leukemic human myeloid cells. Proc Natl Acad Sci U S A. 1986 Feb;83(3):669–673. doi: 10.1073/pnas.83.3.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Gesner T., Mufson R. A., Turner K. J., Clark S. C. Identification through chemical cross-linking of distinct granulocyte-macrophage colony-stimulating factor and interleukin-3 receptors on myeloid leukemic cells, KG-1. Blood. 1989 Dec;74(8):2652–2656. [PubMed] [Google Scholar]
- Goodwin R. G., Friend D., Ziegler S. F., Jerzy R., Falk B. A., Gimpel S., Cosman D., Dower S. K., March C. J., Namen A. E. Cloning of the human and murine interleukin-7 receptors: demonstration of a soluble form and homology to a new receptor superfamily. Cell. 1990 Mar 23;60(6):941–951. doi: 10.1016/0092-8674(90)90342-c. [DOI] [PubMed] [Google Scholar]
- Gough N. M., Gearing D. P., Nicola N. A., Baker E., Pritchard M., Callen D. F., Sutherland G. R. Localization of the human GM-CSF receptor gene to the X-Y pseudoautosomal region. Nature. 1990 Jun 21;345(6277):734–736. doi: 10.1038/345734a0. [DOI] [PubMed] [Google Scholar]
- Groopman J. E., Mitsuyasu R. T., DeLeo M. J., Oette D. H., Golde D. W. Effect of recombinant human granulocyte-macrophage colony-stimulating factor on myelopoiesis in the acquired immunodeficiency syndrome. N Engl J Med. 1987 Sep 3;317(10):593–598. doi: 10.1056/NEJM198709033171003. [DOI] [PubMed] [Google Scholar]
- Grunstein M., Hogness D. S. Colony hybridization: a method for the isolation of cloned DNAs that contain a specific gene. Proc Natl Acad Sci U S A. 1975 Oct;72(10):3961–3965. doi: 10.1073/pnas.72.10.3961. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hatakeyama M., Mori H., Doi T., Taniguchi T. A restricted cytoplasmic region of IL-2 receptor beta chain is essential for growth signal transduction but not for ligand binding and internalization. Cell. 1989 Dec 1;59(5):837–845. doi: 10.1016/0092-8674(89)90607-7. [DOI] [PubMed] [Google Scholar]
- Hayashida K., Kitamura T., Gorman D. M., Arai K., Yokota T., Miyajima A. Molecular cloning of a second subunit of the receptor for human granulocyte-macrophage colony-stimulating factor (GM-CSF): reconstitution of a high-affinity GM-CSF receptor. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9655–9659. doi: 10.1073/pnas.87.24.9655. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Idzerda R. L., March C. J., Mosley B., Lyman S. D., Vanden Bos T., Gimpel S. D., Din W. S., Grabstein K. H., Widmer M. B., Park L. S. Human interleukin 4 receptor confers biological responsiveness and defines a novel receptor superfamily. J Exp Med. 1990 Mar 1;171(3):861–873. doi: 10.1084/jem.171.3.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Itoh N., Yonehara S., Schreurs J., Gorman D. M., Maruyama K., Ishii A., Yahara I., Arai K., Miyajima A. Cloning of an interleukin-3 receptor gene: a member of a distinct receptor gene family. Science. 1990 Jan 19;247(4940):324–327. doi: 10.1126/science.2404337. [DOI] [PubMed] [Google Scholar]
- Jang S. K., Davies M. V., Kaufman R. J., Wimmer E. Initiation of protein synthesis by internal entry of ribosomes into the 5' nontranslated region of encephalomyocarditis virus RNA in vivo. J Virol. 1989 Apr;63(4):1651–1660. doi: 10.1128/jvi.63.4.1651-1660.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mathey-Prevot B., Andrews N. C., Murphy H. S., Kreissman S. G., Nathan D. G. Positive and negative elements regulate human interleukin 3 expression. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5046–5050. doi: 10.1073/pnas.87.13.5046. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Metcalf D., Begley C. G., Williamson D. J., Nice E. C., De Lamarter J., Mermod J. J., Thatcher D., Schmidt A. Hemopoietic responses in mice injected with purified recombinant murine GM-CSF. Exp Hematol. 1987 Jan;15(1):1–9. [PubMed] [Google Scholar]
- Metcalf D., Nicola N. A., Gearing D. P., Gough N. M. Low-affinity placenta-derived receptors for human granulocyte-macrophage colony-stimulating factor can deliver a proliferative signal to murine hemopoietic cells. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4670–4674. doi: 10.1073/pnas.87.12.4670. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Park L. S., Friend D., Gillis S., Urdal D. L. Characterization of the cell surface receptor for granulocyte-macrophage colony-stimulating factor. J Biol Chem. 1986 Mar 25;261(9):4177–4183. [PubMed] [Google Scholar]
- Park L. S., Friend D., Price V., Anderson D., Singer J., Prickett K. S., Urdal D. L. Heterogeneity in human interleukin-3 receptors. A subclass that binds human granulocyte/macrophage colony stimulating factor. J Biol Chem. 1989 Apr 5;264(10):5420–5427. [PubMed] [Google Scholar]
- Park L. S., Waldron P. E., Friend D., Sassenfeld H. M., Price V., Anderson D., Cosman D., Andrews R. G., Bernstein I. D., Urdal D. L. Interleukin-3, GM-CSF, and G-CSF receptor expression on cell lines and primary leukemia cells: receptor heterogeneity and relationship to growth factor responsiveness. Blood. 1989 Jul;74(1):56–65. [PubMed] [Google Scholar]
- 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]
- Sieff C. A., Emerson S. G., Donahue R. E., Nathan D. G., Wang E. A., Wong G. G., Clark S. C. Human recombinant granulocyte-macrophage colony-stimulating factor: a multilineage hematopoietin. Science. 1985 Dec 6;230(4730):1171–1173. doi: 10.1126/science.3877981. [DOI] [PubMed] [Google Scholar]
- Vadhan-Raj S., Keating M., LeMaistre A., Hittelman W. N., McCredie K., Trujillo J. M., Broxmeyer H. E., Henney C., Gutterman J. U. Effects of recombinant human granulocyte-macrophage colony-stimulating factor in patients with myelodysplastic syndromes. N Engl J Med. 1987 Dec 17;317(25):1545–1552. doi: 10.1056/NEJM198712173172501. [DOI] [PubMed] [Google Scholar]
- Walker F., Burgess A. W. Specific binding of radioiodinated granulocyte-macrophage colony-stimulating factor to hemopoietic cells. EMBO J. 1985 Apr;4(4):933–939. doi: 10.1002/j.1460-2075.1985.tb03721.x. [DOI] [PMC free article] [PubMed] [Google Scholar]