Abstract
Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays an important role in hematopoiesis and host defense via interaction with specific cell-surface receptors in target tissues. We identified a truncated, soluble form of the low-affinity GM-CSF receptor (GMR) in chorio-carcinoma cells. Low-affinity GMR cDNAs encoding both the membrane-bound and soluble receptors were obtained by PCR using primers corresponding to the published sequence. Clones encoding the soluble receptor were identical in sequence to the membrane-bound form but contained a 97-nucleotide internal deletion. The amino acid sequence of this deleted cDNA predicts a protein that lacks the 84 C-terminal amino acids of the membrane-bound receptor, including the transmembrane and cytoplasmic domains, and contains 16 different amino acids at its C terminus. Expression of the soluble GMR cDNA in murine psi-AM cells as well as GM-CSF-dependent myeloid 32Dc13 cells produced a secreted protein that retained its capacity to bind GM-CSF in solution. RNase protection analysis indicates that this variant cDNA is derived from a naturally occurring mRNA. Soluble receptors have been identified for several other hematopoietin receptors and may be a general feature of this class. The striking similarity between the soluble form of the GMR and other hematopoietin receptors suggests that soluble binding proteins may play an important role in regulating the broad spectrum of biological responses mediated by these cytokines.
Full text
PDFImages 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]
- Baldwin G. C., Gasson J. C., Kaufman S. E., Quan S. G., Williams R. E., Avalos B. R., Gazdar A. F., Golde D. W., DiPersio J. F. Nonhematopoietic tumor cells express functional GM-CSF receptors. Blood. 1989 Mar;73(4):1033–1037. [PubMed] [Google Scholar]
- Basu A., Raghunath M., Bishayee S., Das M. Inhibition of tyrosine kinase activity of the epidermal growth factor (EGF) receptor by a truncated receptor form that binds to EGF: role for interreceptor interaction in kinase regulation. Mol Cell Biol. 1989 Feb;9(2):671–677. doi: 10.1128/mcb.9.2.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Baumbach W. R., Horner D. L., Logan J. S. The growth hormone-binding protein in rat serum is an alternatively spliced form of the rat growth hormone receptor. Genes Dev. 1989 Aug;3(8):1199–1205. doi: 10.1101/gad.3.8.1199. [DOI] [PubMed] [Google Scholar]
- Bazan J. F. Haemopoietic receptors and helical cytokines. Immunol Today. 1990 Oct;11(10):350–354. doi: 10.1016/0167-5699(90)90139-z. [DOI] [PubMed] [Google Scholar]
- 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]
- Bussolino F., Wang J. M., Defilippi P., Turrini F., Sanavio F., Edgell C. J., Aglietta M., Arese P., Mantovani A. Granulocyte- and granulocyte-macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature. 1989 Feb 2;337(6206):471–473. doi: 10.1038/337471a0. [DOI] [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]
- Cone R. D., Mulligan R. C. High-efficiency gene transfer into mammalian cells: generation of helper-free recombinant retrovirus with broad mammalian host range. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6349–6353. doi: 10.1073/pnas.81.20.6349. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dedhar S., Gaboury L., Galloway P., Eaves C. Human granulocyte-macrophage colony-stimulating factor is a growth factor active on a variety of cell types of nonhemopoietic origin. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9253–9257. doi: 10.1073/pnas.85.23.9253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DiPersio J. F., Hedvat C., Ford C. F., Golde D. W., Gasson J. C. Characterization of the soluble human granulocyte-macrophage colony-stimulating factor receptor complex. J Biol Chem. 1991 Jan 5;266(1):279–286. [PubMed] [Google Scholar]
- DiStefano P. S., Johnson E. M., Jr Identification of a truncated form of the nerve growth factor receptor. Proc Natl Acad Sci U S A. 1988 Jan;85(1):270–274. doi: 10.1073/pnas.85.1.270. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Downing J. R., Roussel M. F., Sherr C. J. Ligand and protein kinase C downmodulate the colony-stimulating factor 1 receptor by independent mechanisms. Mol Cell Biol. 1989 Jul;9(7):2890–2896. doi: 10.1128/mcb.9.7.2890. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Early P., Rogers J., Davis M., Calame K., Bond M., Wall R., Hood L. Two mRNAs can be produced from a single immunoglobulin mu gene by alternative RNA processing pathways. Cell. 1980 Jun;20(2):313–319. doi: 10.1016/0092-8674(80)90617-0. [DOI] [PubMed] [Google Scholar]
- Fernandez-Botran R., Vitetta E. S. A soluble, high-affinity, interleukin-4-binding protein is present in the biological fluids of mice. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4202–4206. doi: 10.1073/pnas.87.11.4202. [DOI] [PMC free article] [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]
- Gasson J. C. Molecular physiology of granulocyte-macrophage colony-stimulating factor. Blood. 1991 Mar 15;77(6):1131–1145. [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]
- 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]
- Gray P. W., Barrett K., Chantry D., Turner M., Feldmann M. Cloning of human tumor necrosis factor (TNF) receptor cDNA and expression of recombinant soluble TNF-binding protein. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7380–7384. doi: 10.1073/pnas.87.19.7380. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Greenberger J. S., Sakakeeny M. A., Humphries R. K., Eaves C. J., Eckner R. J. Demonstration of permanent factor-dependent multipotential (erythroid/neutrophil/basophil) hematopoietic progenitor cell lines. Proc Natl Acad Sci U S A. 1983 May;80(10):2931–2935. doi: 10.1073/pnas.80.10.2931. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gubler U., Hoffman B. J. A simple and very efficient method for generating cDNA libraries. Gene. 1983 Nov;25(2-3):263–269. doi: 10.1016/0378-1119(83)90230-5. [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]
- 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]
- Kohno T., Brewer M. T., Baker S. L., Schwartz P. E., King M. W., Hale K. K., Squires C. H., Thompson R. C., Vannice J. L. A second tumor necrosis factor receptor gene product can shed a naturally occurring tumor necrosis factor inhibitor. Proc Natl Acad Sci U S A. 1990 Nov;87(21):8331–8335. doi: 10.1073/pnas.87.21.8331. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maihle N. J., Flickinger T. W., Raines M. A., Sanders M. L., Kung H. J. Native avian c-erbB gene expresses a secreted protein product corresponding to the ligand-binding domain of the receptor. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1825–1829. doi: 10.1073/pnas.88.5.1825. [DOI] [PMC free article] [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]
- Miller A. D., Rosman G. J. Improved retroviral vectors for gene transfer and expression. Biotechniques. 1989 Oct;7(9):980-2, 984-6, 989-90. [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]
- Novick D., Engelmann H., Wallach D., Leitner O., Revel M., Rubinstein M. Purification of soluble cytokine receptors from normal human urine by ligand-affinity and immunoaffinity chromatography. J Chromatogr. 1990 Jun 27;510:331–337. doi: 10.1016/s0021-9673(01)93767-7. [DOI] [PubMed] [Google Scholar]
- Novick D., Engelmann H., Wallach D., Rubinstein M. Soluble cytokine receptors are present in normal human urine. J Exp Med. 1989 Oct 1;170(4):1409–1414. doi: 10.1084/jem.170.4.1409. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Park L. S., Friend D., Gillis S., Urdal D. L. Characterization of the cell surface receptor for human granulocyte/macrophage colony-stimulating factor. J Exp Med. 1986 Jul 1;164(1):251–262. doi: 10.1084/jem.164.1.251. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Raines M. A., Maihle N. J., Moscovici C., Moscovici M. G., Kung H. J. Molecular characterization of three erbB transducing viruses generated during avian leukosis virus-induced erythroleukemia: extensive internal deletion near the kinase domain activates the fibrosarcoma- and hemangioma-inducing potentials of erbB. J Virol. 1988 Jul;62(7):2444–2452. doi: 10.1128/jvi.62.7.2444-2452.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Robb R. J., Kutny R. M. Structure-function relationships for the IL 2-receptor system. IV. Analysis of the sequence and ligand-binding properties of soluble Tac protein. J Immunol. 1987 Aug 1;139(3):855–862. [PubMed] [Google Scholar]
- Symons J. A., Duff G. W. A soluble form of the interleukin-1 receptor produced by a human B cell line. FEBS Lett. 1990 Oct 15;272(1-2):133–136. doi: 10.1016/0014-5793(90)80466-v. [DOI] [PubMed] [Google Scholar]
- Takaki S., Tominaga A., Hitoshi Y., Mita S., Sonoda E., Yamaguchi N., Takatsu K. Molecular cloning and expression of the murine interleukin-5 receptor. EMBO J. 1990 Dec;9(13):4367–4374. doi: 10.1002/j.1460-2075.1990.tb07886.x. [DOI] [PMC free article] [PubMed] [Google Scholar]