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. 1993 Oct;4(10):983–992. doi: 10.1091/mbc.4.10.983

Differential regulation of early response genes and cell proliferation through the human granulocyte macrophage colony-stimulating factor receptor: selective activation of the c-fos promoter by genistein.

S Watanabe 1, A Muto 1, T Yokota 1, A Miyajima 1, K Arai 1
PMCID: PMC275732  PMID: 8298195

Abstract

Granulocyte macrophage colony-stimulating factor (GM-CSF) binds to the high-affinity GM-CSF receptor (GMR) consisting of alpha and beta subunits and induces rapid tyrosine phosphorylation, activation of early response genes, and proliferation of hematopoietic cells. The alpha subunit is the primary cytokine binding component and the beta subunit is required for high-affinity binding as well as for signal transduction. Using tyrosine kinase inhibitors and cytoplasmic deletion mutants of the beta subunit, we obtained evidence that there are at least two distinct pathways downstream of the GMR in BA/F3 cell, one which is essential for proliferation, leads to the c-myc gene activation, and is sensitive to herbimycin and genistein. Activation of this pathway depends on the cytoplasmic region between amino acid positions 455 and 517 of the beta subunit. The second pathway, which leads to activation of c-fos and c-jun genes, is only partially sensitive to herbimycin, is resistant to genistein and depends on the region between amino acid positions 626 and 763 of the beta subunit. Unexpectedly, the c-fos mRNA induction was augmented by genistein. The enhanced expression of c-fos mRNA by genistein also occurred with stimulation with cAMP, PMA, or EGF in NIH3T3 cells. It thus seems likely that genistein affects a common pathway downstream of these signals.

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Selected References

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

  1. Angel P., Karin M. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta. 1991 Dec 10;1072(2-3):129–157. doi: 10.1016/0304-419x(91)90011-9. [DOI] [PubMed] [Google Scholar]
  2. Arai K. I., Lee F., Miyajima A., Miyatake S., Arai N., Yokota T. Cytokines: coordinators of immune and inflammatory responses. Annu Rev Biochem. 1990;59:783–836. doi: 10.1146/annurev.bi.59.070190.004031. [DOI] [PubMed] [Google Scholar]
  3. Badwey J. A., Erickson R. W., Curnutte J. T. Staurosporine inhibits the soluble and membrane-bound protein tyrosine kinases of human neutrophils. Biochem Biophys Res Commun. 1991 Jul 31;178(2):423–429. doi: 10.1016/0006-291x(91)90124-p. [DOI] [PubMed] [Google Scholar]
  4. Chen C. Y., You Y., Shyu A. B. Two cellular proteins bind specifically to a purine-rich sequence necessary for the destabilization function of a c-fos protein-coding region determinant of mRNA instability. Mol Cell Biol. 1992 Dec;12(12):5748–5757. doi: 10.1128/mcb.12.12.5748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Eder M., Griffin J. D., Ernst T. J. The human granulocyte-macrophage colony-stimulating factor receptor is capable of initiating signal transduction in NIH3T3 cells. EMBO J. 1993 Apr;12(4):1647–1656. doi: 10.1002/j.1460-2075.1993.tb05810.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gille H., Sharrocks A. D., Shaw P. E. Phosphorylation of transcription factor p62TCF by MAP kinase stimulates ternary complex formation at c-fos promoter. Nature. 1992 Jul 30;358(6385):414–417. doi: 10.1038/358414a0. [DOI] [PubMed] [Google Scholar]
  7. Gotoh Y., Nishida E., Yamashita T., Hoshi M., Kawakami M., Sakai H. Microtubule-associated-protein (MAP) kinase activated by nerve growth factor and epidermal growth factor in PC12 cells. Identity with the mitogen-activated MAP kinase of fibroblastic cells. Eur J Biochem. 1990 Nov 13;193(3):661–669. doi: 10.1111/j.1432-1033.1990.tb19384.x. [DOI] [PubMed] [Google Scholar]
  8. Greenberg M. E., Greene L. A., Ziff E. B. Nerve growth factor and epidermal growth factor induce rapid transient changes in proto-oncogene transcription in PC12 cells. J Biol Chem. 1985 Nov 15;260(26):14101–14110. [PubMed] [Google Scholar]
  9. Greenberg M. E., Ziff E. B. Stimulation of 3T3 cells induces transcription of the c-fos proto-oncogene. Nature. 1984 Oct 4;311(5985):433–438. doi: 10.1038/311433a0. [DOI] [PubMed] [Google Scholar]
  10. Hanazono Y., Chiba S., Sasaki K., Mano H., Miyajima A., Arai K., Yazaki Y., Hirai H. c-fps/fes protein-tyrosine kinase is implicated in a signaling pathway triggered by granulocyte-macrophage colony-stimulating factor and interleukin-3. EMBO J. 1993 Apr;12(4):1641–1646. doi: 10.1002/j.1460-2075.1993.tb05809.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hara T., Miyajima A. Two distinct functional high affinity receptors for mouse interleukin-3 (IL-3). EMBO J. 1992 May;11(5):1875–1884. doi: 10.1002/j.1460-2075.1992.tb05239.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hatakeyama M., Kawahara A., Mori H., Shibuya H., Taniguchi T. c-fos gene induction by interleukin 2: identification of the critical cytoplasmic regions within the interleukin 2 receptor beta chain. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2022–2026. doi: 10.1073/pnas.89.6.2022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Holt J. T., Gopal T. V., Moulton A. D., Nienhuis A. W. Inducible production of c-fos antisense RNA inhibits 3T3 cell proliferation. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4794–4798. doi: 10.1073/pnas.83.13.4794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Huang J., Nasr M., Kim Y., Matthews H. R. Genistein inhibits protein histidine kinase. J Biol Chem. 1992 Aug 5;267(22):15511–15515. [PubMed] [Google Scholar]
  17. Isfort R. J., Stevens D., May W. S., Ihle J. N. Interleukin 3 binds to a 140-kDa phosphotyrosine-containing cell surface protein. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7982–7986. doi: 10.1073/pnas.85.21.7982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Isfort R., Huhn R. D., Frackelton A. R., Jr, Ihle J. N. Stimulation of factor-dependent myeloid cell lines with interleukin 3 induces tyrosine phosphorylation of several cellular substrates. J Biol Chem. 1988 Dec 15;263(35):19203–19209. [PubMed] [Google Scholar]
  19. 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]
  20. Kanakura Y., Druker B., Cannistra S. A., Furukawa Y., Torimoto Y., Griffin J. D. Signal transduction of the human granulocyte-macrophage colony-stimulating factor and interleukin-3 receptors involves tyrosine phosphorylation of a common set of cytoplasmic proteins. Blood. 1990 Aug 15;76(4):706–715. [PubMed] [Google Scholar]
  21. Kitamura T., Sato N., Arai K., Miyajima A. Expression cloning of the human IL-3 receptor cDNA reveals a shared beta subunit for the human IL-3 and GM-CSF receptors. Cell. 1991 Sep 20;66(6):1165–1174. doi: 10.1016/0092-8674(91)90039-2. [DOI] [PubMed] [Google Scholar]
  22. Lee F., Yokota T., Otsuka T., Gemmell L., Larson N., Luh J., Arai K., Rennick D. Isolation of cDNA for a human granulocyte-macrophage colony-stimulating factor by functional expression in mammalian cells. Proc Natl Acad Sci U S A. 1985 Jul;82(13):4360–4364. doi: 10.1073/pnas.82.13.4360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lucibello F. C., Lowag C., Neuberg M., Müller R. trans-repression of the mouse c-fos promoter: a novel mechanism of Fos-mediated trans-regulation. Cell. 1989 Dec 22;59(6):999–1007. doi: 10.1016/0092-8674(89)90756-3. [DOI] [PubMed] [Google Scholar]
  24. Manak J. R., de Bisschop N., Kris R. M., Prywes R. Casein kinase II enhances the DNA binding activity of serum response factor. Genes Dev. 1990 Jun;4(6):955–967. doi: 10.1101/gad.4.6.955. [DOI] [PubMed] [Google Scholar]
  25. Marais R. M., Hsuan J. J., McGuigan C., Wynne J., Treisman R. Casein kinase II phosphorylation increases the rate of serum response factor-binding site exchange. EMBO J. 1992 Jan;11(1):97–105. doi: 10.1002/j.1460-2075.1992.tb05032.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Marcu K. B., Bossone S. A., Patel A. J. myc function and regulation. Annu Rev Biochem. 1992;61:809–860. doi: 10.1146/annurev.bi.61.070192.004113. [DOI] [PubMed] [Google Scholar]
  27. Minami Y., Kono T., Yamada K., Kobayashi N., Kawahara A., Perlmutter R. M., Taniguchi T. Association of p56lck with IL-2 receptor beta chain is critical for the IL-2-induced activation of p56lck. EMBO J. 1993 Feb;12(2):759–768. doi: 10.1002/j.1460-2075.1993.tb05710.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Miyajima A., Kitamura T., Harada N., Yokota T., Arai K. Cytokine receptors and signal transduction. Annu Rev Immunol. 1992;10:295–331. doi: 10.1146/annurev.iy.10.040192.001455. [DOI] [PubMed] [Google Scholar]
  29. Miyajima A., Schreurs J., Otsu K., Kondo A., Arai K., Maeda S. Use of the silkworm, Bombyx mori, and an insect baculovirus vector for high-level expression and secretion of biologically active mouse interleukin-3. Gene. 1987;58(2-3):273–281. doi: 10.1016/0378-1119(87)90382-9. [DOI] [PubMed] [Google Scholar]
  30. Ofir R., Dwarki V. J., Rashid D., Verma I. M. Phosphorylation of the C terminus of Fos protein is required for transcriptional transrepression of the c-fos promoter. Nature. 1990 Nov 1;348(6296):80–82. doi: 10.1038/348080a0. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. Sakamaki K., Miyajima I., Kitamura T., Miyajima A. Critical cytoplasmic domains of the common beta subunit of the human GM-CSF, IL-3 and IL-5 receptors for growth signal transduction and tyrosine phosphorylation. EMBO J. 1992 Oct;11(10):3541–3549. doi: 10.1002/j.1460-2075.1992.tb05437.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Satoh T., Uehara Y., Kaziro Y. Inhibition of interleukin 3 and granulocyte-macrophage colony-stimulating factor stimulated increase of active ras.GTP by herbimycin A, a specific inhibitor of tyrosine kinases. J Biol Chem. 1992 Feb 5;267(4):2537–2541. [PubMed] [Google Scholar]
  34. Schönthal A., Herrlich P., Rahmsdorf H. J., Ponta H. Requirement for fos gene expression in the transcriptional activation of collagenase by other oncogenes and phorbol esters. Cell. 1988 Jul 29;54(3):325–334. doi: 10.1016/0092-8674(88)90195-x. [DOI] [PubMed] [Google Scholar]
  35. Shyu A. B., Greenberg M. E., Belasco J. G. The c-fos transcript is targeted for rapid decay by two distinct mRNA degradation pathways. Genes Dev. 1989 Jan;3(1):60–72. doi: 10.1101/gad.3.1.60. [DOI] [PubMed] [Google Scholar]
  36. Torigoe T., O'Connor R., Santoli D., Reed J. C. Interleukin-3 regulates the activity of the LYN protein-tyrosine kinase in myeloid-committed leukemic cell lines. Blood. 1992 Aug 1;80(3):617–624. [PubMed] [Google Scholar]
  37. Watanabe S., Mui A. L., Muto A., Chen J. X., Hayashida K., Yokota T., Miyajima A., Arai K. Reconstituted human granulocyte-macrophage colony-stimulating factor receptor transduces growth-promoting signals in mouse NIH 3T3 cells: comparison with signalling in BA/F3 pro-B cells. Mol Cell Biol. 1993 Mar;13(3):1440–1448. doi: 10.1128/mcb.13.3.1440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Watanabe S., Nakayama N., Yokota T., Arai K., Miyajima A. Colony-stimulating factors and cytokine receptor network. Curr Opin Biotechnol. 1991 Apr;2(2):227–237. doi: 10.1016/0958-1669(91)90015-w. [DOI] [PubMed] [Google Scholar]
  39. Welham M. J., Duronio V., Sanghera J. S., Pelech S. L., Schrader J. W. Multiple hemopoietic growth factors stimulate activation of mitogen-activated protein kinase family members. J Immunol. 1992 Sep 1;149(5):1683–1693. [PubMed] [Google Scholar]
  40. Yang Y. C., Ciarletta A. B., Temple P. A., Chung M. P., Kovacic S., Witek-Giannotti J. S., Leary A. C., Kriz R., Donahue R. E., Wong G. G. Human IL-3 (multi-CSF): identification by expression cloning of a novel hematopoietic growth factor related to murine IL-3. Cell. 1986 Oct 10;47(1):3–10. doi: 10.1016/0092-8674(86)90360-0. [DOI] [PubMed] [Google Scholar]

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