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. 1993 Jul 15;90(14):6721–6725. doi: 10.1073/pnas.90.14.6721

The serum response element can mediate induction of c-fos by growth hormone.

D J Meyer 1, E W Stephenson 1, L Johnson 1, B H Cochran 1, J Schwartz 1
PMCID: PMC47004  PMID: 8341690

Abstract

The c-fos protooncogene is transcriptionally activated by a wide variety of agents including serum, growth factors, and phorbol esters. This induction is rapid and transient and is mediated through a number of identified promoter elements. Growth hormone (GH) is also known to induce transcription of c-fos in a variety of cell types including NIH 3T3 fibroblasts and 3T3-F442A preadipocytes. To identify DNA sequences in the c-fos gene regulated by GH, this study sought to determine whether induction of c-fos by GH involves previously identified c-fos promoter elements. A plasmid containing a growth factor-sensitive fragment of the upstream region of the c-fos promoter from -361 to -264 bp was tested for GH sensitivity. The fragment was cloned upstream of a human c-fos reporter [designated FOS by Human Gene Mapping 11 (1991)], which included basal promoter elements. In transiently transfected mouse NIH 3T3 fibroblasts, the promoter fragment conferred GH sensitivity on the human c-fos reporter. To identify a specific GH-sensitive DNA sequence in this promoter, a serum response element (SRE)-reporter plasmid was tested and found to be stimulated by GH. GH was effective in inducing expression through the SRE over a range of physiological GH concentrations. Since GH was recently found to synergize with serum factors in inducing c-fos transcription, the effect of GH and serum on SRE function was examined for insight into the mechanism for such synergism. The combined effect of GH and serum to induce reporter expression through the SRE was greater than the added effects of GH and serum, indicating that the synergism between GH and serum in inducing c-fos involves the SRE sequence. These studies identify the SRE as one specific DNA sequence in the c-fos promoter functionally regulated by GH. It is notable that GH is effective at physiological concentrations. Furthermore, synergism in c-fos induction between GH and serum factors is evident through the SRE.

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Selected References

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

  1. Ashcom G., Gurland G., Schwartz J. Growth hormone synergizes with serum growth factors in inducing c-fos transcription in 3T3-F442A cells. Endocrinology. 1992 Oct;131(4):1915–1921. doi: 10.1210/endo.131.4.1396336. [DOI] [PubMed] [Google Scholar]
  2. Campbell G. S., Pang L., Miyasaka T., Saltiel A. R., Carter-Su C. Stimulation by growth hormone of MAP kinase activity in 3T3-F442A fibroblasts. J Biol Chem. 1992 Mar 25;267(9):6074–6080. [PubMed] [Google Scholar]
  3. 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]
  4. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Distel R. J., Ro H. S., Rosen B. S., Groves D. L., Spiegelman B. M. Nucleoprotein complexes that regulate gene expression in adipocyte differentiation: direct participation of c-fos. Cell. 1987 Jun 19;49(6):835–844. doi: 10.1016/0092-8674(87)90621-0. [DOI] [PubMed] [Google Scholar]
  7. Doglio A., Dani C., Grimaldi P., Ailhaud G. Growth hormone stimulates c-fos gene expression by means of protein kinase C without increasing inositol lipid turnover. Proc Natl Acad Sci U S A. 1989 Feb;86(4):1148–1152. doi: 10.1073/pnas.86.4.1148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Edén S. Age- and sex-related differences in episodic growth hormone secretion in the rat. Endocrinology. 1979 Aug;105(2):555–560. doi: 10.1210/endo-105-2-555. [DOI] [PubMed] [Google Scholar]
  9. Fisch T. M., Prywes R., Roeder R. G. An AP1-binding site in the c-fos gene can mediate induction by epidermal growth factor and 12-O-tetradecanoyl phorbol-13-acetate. Mol Cell Biol. 1989 Mar;9(3):1327–1331. doi: 10.1128/mcb.9.3.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Foster C. M., Shafer J. A., Rozsa F. W., Wang X. Y., Lewis S. D., Renken D. A., Natale J. E., Schwartz J., Carter-Su C. Growth hormone promoted tyrosyl phosphorylation of growth hormone receptors in murine 3T3-F442A fibroblasts and adipocytes. Biochemistry. 1988 Jan 12;27(1):326–334. doi: 10.1021/bi00401a049. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Graham R., Gilman M. Distinct protein targets for signals acting at the c-fos serum response element. Science. 1991 Jan 11;251(4990):189–192. doi: 10.1126/science.1898992. [DOI] [PubMed] [Google Scholar]
  13. Greenberg M. E., Siegfried Z., Ziff E. B. Mutation of the c-fos gene dyad symmetry element inhibits serum inducibility of transcription in vivo and the nuclear regulatory factor binding in vitro. Mol Cell Biol. 1987 Mar;7(3):1217–1225. doi: 10.1128/mcb.7.3.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gurland G., Ashcom G., Cochran B. H., Schwartz J. Rapid events in growth hormone action. Induction of c-fos and c-jun transcription in 3T3-F442A preadipocytes. Endocrinology. 1990 Dec;127(6):3187–3195. doi: 10.1210/endo-127-6-3187. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Hatakeyama M., Kono T., Kobayashi N., Kawahara A., Levin S. D., Perlmutter R. M., Taniguchi T. Interaction of the IL-2 receptor with the src-family kinase p56lck: identification of novel intermolecular association. Science. 1991 Jun 14;252(5012):1523–1528. doi: 10.1126/science.2047859. [DOI] [PubMed] [Google Scholar]
  17. Hayes T. E., Kitchen A. M., Cochran B. H. Inducible binding of a factor to the c-fos regulatory region. Proc Natl Acad Sci U S A. 1987 Mar;84(5):1272–1276. doi: 10.1073/pnas.84.5.1272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hayes T. E., Sengupta P., Cochran B. H. The human c-fos serum response factor and the yeast factors GRM/PRTF have related DNA-binding specificities. Genes Dev. 1988 Dec;2(12B):1713–1722. doi: 10.1101/gad.2.12b.1713. [DOI] [PubMed] [Google Scholar]
  19. Herrera R. E., Shaw P. E., Nordheim A. Occupation of the c-fos serum response element in vivo by a multi-protein complex is unaltered by growth factor induction. Nature. 1989 Jul 6;340(6228):68–70. doi: 10.1038/340068a0. [DOI] [PubMed] [Google Scholar]
  20. Malik R. K., Roe M. W., Blackshear P. J. Epidermal growth factor and other mitogens induce binding of a protein complex to the c-fos serum response element in human astrocytoma and other cells. J Biol Chem. 1991 May 5;266(13):8576–8582. [PubMed] [Google Scholar]
  21. 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]
  22. 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]
  23. Morikawa M., Nixon T., Green H. Growth hormone and the adipose conversion of 3T3 cells. Cell. 1982 Jul;29(3):783–789. doi: 10.1016/0092-8674(82)90440-8. [DOI] [PubMed] [Google Scholar]
  24. Nixon T., Green H. Contribution of growth hormone to the adipogenic activity of serum. Endocrinology. 1984 Feb;114(2):527–532. doi: 10.1210/endo-114-2-527. [DOI] [PubMed] [Google Scholar]
  25. Rauscher F. J., 3rd, Sambucetti L. C., Curran T., Distel R. J., Spiegelman B. M. Common DNA binding site for Fos protein complexes and transcription factor AP-1. Cell. 1988 Feb 12;52(3):471–480. doi: 10.1016/s0092-8674(88)80039-4. [DOI] [PubMed] [Google Scholar]
  26. Rui H., Djeu J. Y., Evans G. A., Kelly P. A., Farrar W. L. Prolactin receptor triggering. Evidence for rapid tyrosine kinase activation. J Biol Chem. 1992 Nov 25;267(33):24076–24081. [PubMed] [Google Scholar]
  27. Sheng M., Dougan S. T., McFadden G., Greenberg M. E. Calcium and growth factor pathways of c-fos transcriptional activation require distinct upstream regulatory sequences. Mol Cell Biol. 1988 Jul;8(7):2787–2796. doi: 10.1128/mcb.8.7.2787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Siegfried Z., Ziff E. B. Transcription activation by serum, PDGF, and TPA through the c-fos DSE: cell type specific requirements for induction. Oncogene. 1989 Jan;4(1):3–11. [PubMed] [Google Scholar]
  29. Slootweg M. C., de Groot R. P., Herrmann-Erlee M. P., Koornneef I., Kruijer W., Kramer Y. M. Growth hormone induces expression of c-jun and jun B oncogenes and employs a protein kinase C signal transduction pathway for the induction of c-fos oncogene expression. J Mol Endocrinol. 1991 Apr;6(2):179–188. doi: 10.1677/jme.0.0060179. [DOI] [PubMed] [Google Scholar]
  30. Stred S. E., Stubbart J. R., Argetsinger L. S., Smith W. C., Shafer J. A., Talamantes F., Carter-Su C. Stimulation by growth hormone (GH) of GH receptor-associated tyrosine kinase activity. Endocrinology. 1992 Mar;130(3):1626–1636. doi: 10.1210/endo.130.3.1537311. [DOI] [PubMed] [Google Scholar]
  31. Stumpo D. J., Stewart T. N., Gilman M. Z., Blackshear P. J. Identification of c-fos sequences involved in induction by insulin and phorbol esters. J Biol Chem. 1988 Feb 5;263(4):1611–1614. [PubMed] [Google Scholar]
  32. Sumantran V. N., Tsai M. L., Schwartz J. Growth hormone induces c-fos and c-jun expression in cells with varying requirements for differentiation. Endocrinology. 1992 Apr;130(4):2016–2024. doi: 10.1210/endo.130.4.1547725. [DOI] [PubMed] [Google Scholar]
  33. Tannenbaum G. S., Martin J. B. Evidence for an endogenous ultradian rhythm governing growth hormone secretion in the rat. Endocrinology. 1976 Mar;98(3):562–570. doi: 10.1210/endo-98-3-562. [DOI] [PubMed] [Google Scholar]
  34. Tollet P., Legraverend C., Gustafsson J. A., Mode A. A role for protein kinases in the growth hormone regulation of cytochrome P4502C12 and insulin-like growth factor-I messenger RNA expression in primary adult rat hepatocytes. Mol Endocrinol. 1991 Sep;5(9):1351–1358. doi: 10.1210/mend-5-9-1351. [DOI] [PubMed] [Google Scholar]
  35. Treisman R. The serum response element. Trends Biochem Sci. 1992 Oct;17(10):423–426. doi: 10.1016/0968-0004(92)90013-y. [DOI] [PubMed] [Google Scholar]
  36. Treisman R. Transient accumulation of c-fos RNA following serum stimulation requires a conserved 5' element and c-fos 3' sequences. Cell. 1985 Oct;42(3):889–902. doi: 10.1016/0092-8674(85)90285-5. [DOI] [PubMed] [Google Scholar]
  37. Visvader J., Sassone-Corsi P., Verma I. M. Two adjacent promoter elements mediate nerve growth factor activation of the c-fos gene and bind distinct nuclear complexes. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9474–9478. doi: 10.1073/pnas.85.24.9474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wagner B. J., Hayes T. E., Hoban C. J., Cochran B. H. The SIF binding element confers sis/PDGF inducibility onto the c-fos promoter. EMBO J. 1990 Dec;9(13):4477–4484. doi: 10.1002/j.1460-2075.1990.tb07898.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Winston L. A., Bertics P. J. Growth hormone stimulates the tyrosine phosphorylation of 42- and 45-kDa ERK-related proteins. J Biol Chem. 1992 Mar 5;267(7):4747–4751. [PubMed] [Google Scholar]
  40. Yoon J. B., Berry S. A., Seelig S., Towle H. C. An inducible nuclear factor binds to a growth hormone-regulated gene. J Biol Chem. 1990 Nov 15;265(32):19947–19954. [PubMed] [Google Scholar]
  41. Yoshimura A., Lodish H. F. In vitro phosphorylation of the erythropoietin receptor and an associated protein, pp130. Mol Cell Biol. 1992 Feb;12(2):706–715. doi: 10.1128/mcb.12.2.706. [DOI] [PMC free article] [PubMed] [Google Scholar]

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