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. 1988 Jul;85(14):5031–5035. doi: 10.1073/pnas.85.14.5031

Isolation of a cDNA clone encoding a biologically active thyroid hormone receptor.

R J Koenig 1, R L Warne 1, G A Brent 1, J W Harney 1, P R Larsen 1, D D Moore 1
PMCID: PMC281681  PMID: 2899322

Abstract

We have isolated a c-erbA cDNA clone from a GH3 cell library. The clone, denoted erb62, is 4.5 kilobases long and encodes a 461-amino acid beta-type c-erbA protein. This c-erbA protein binds 3,5,3'-triiodothyronine (T3) and T3 analogs with affinities similar to those of the authentic T3 receptor. By RNA gel blot analysis, erb62 hybridizes to a 6-kilobase RNA found in organs that express T3 receptors--e.g., heart, kidney, and brain. A COS-cell transient cotransfection system was used to show that erb62 encodes a biologically active T3 receptor. An oligonucleotide, corresponding to a portion of the rat growth hormone gene 5'-flanking region that contains a T3 response element, was inserted on the 5' side of the herpes simplex virus thymidine kinase promoter in a chloramphenicol acetyltransferase-expressing plasmid. Reporter gene expression directed by this hybrid promoter was T3 inducible only if this plasmid was cotransfected with an erb62-expressing plasmid.

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Selected References

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

  1. Aruffo A., Seed B. Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8573–8577. doi: 10.1073/pnas.84.23.8573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benbrook D., Pfahl M. A novel thyroid hormone receptor encoded by a cDNA clone from a human testis library. Science. 1987 Nov 6;238(4828):788–791. doi: 10.1126/science.3672126. [DOI] [PubMed] [Google Scholar]
  3. Cattini P. A., Eberhardt N. L. Regulated expression of chimaeric genes containing the 5'-flanking regions of human growth hormone-related genes in transiently transfected rat anterior pituitary tumor cells. Nucleic Acids Res. 1987 Feb 11;15(3):1297–1309. doi: 10.1093/nar/15.3.1297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chen E. Y., Seeburg P. H. Supercoil sequencing: a fast and simple method for sequencing plasmid DNA. DNA. 1985 Apr;4(2):165–170. doi: 10.1089/dna.1985.4.165. [DOI] [PubMed] [Google Scholar]
  5. Crew M. D., Spindler S. R. Thyroid hormone regulation of the transfected rat growth hormone promoter. J Biol Chem. 1986 Apr 15;261(11):5018–5022. [PubMed] [Google Scholar]
  6. Dayton A. I., Selden J. R., Laws G., Dorney D. J., Finan J., Tripputi P., Emanuel B. S., Rovera G., Nowell P. C., Croce C. M. A human c-erbA oncogene homologue is closely proximal to the chromosome 17 breakpoint in acute promyelocytic leukemia. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4495–4499. doi: 10.1073/pnas.81.14.4495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Diamond D. J., Goodman H. M. Regulation of growth hormone messenger RNA synthesis by dexamethasone and triiodothyronine. Transcriptional rate and mRNA stability changes in pituitary tumor cells. J Mol Biol. 1985 Jan 5;181(1):41–62. doi: 10.1016/0022-2836(85)90323-7. [DOI] [PubMed] [Google Scholar]
  8. Dozin B., Magnuson M. A., Nikodem V. M. Thyroid hormone regulation of malic enzyme synthesis. Dual tissue-specific control. J Biol Chem. 1986 Aug 5;261(22):10290–10292. [PubMed] [Google Scholar]
  9. Flug F., Copp R. P., Casanova J., Horowitz Z. D., Janocko L., Plotnick M., Samuels H. H. cis-acting elements of the rat growth hormone gene which mediate basal and regulated expression by thyroid hormone. J Biol Chem. 1987 May 5;262(13):6373–6382. [PubMed] [Google Scholar]
  10. Glass C. K., Franco R., Weinberger C., Albert V. R., Evans R. M., Rosenfeld M. G. A c-erb-A binding site in rat growth hormone gene mediates trans-activation by thyroid hormone. Nature. 1987 Oct 22;329(6141):738–741. doi: 10.1038/329738a0. [DOI] [PubMed] [Google Scholar]
  11. Hartong R., Wiersinga W. M., Lamers W. H. Nuclear 3,5,3'-triiodothyronine receptor occupancy, phosphoenolpyruvate carboxykinase (PEPck) messenger ribonucleic acid levels and PEPck enzyme activity in rat liver. Endocrinology. 1987 Jun;120(6):2460–2467. doi: 10.1210/endo-120-6-2460. [DOI] [PubMed] [Google Scholar]
  12. Jacoby D. B., Engle J. A., Towle H. C. Induction of a rapidly responsive hepatic gene product by thyroid hormone requires ongoing protein synthesis. Mol Cell Biol. 1987 Apr;7(4):1352–1357. doi: 10.1128/mcb.7.4.1352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Koenig R. J., Brent G. A., Warne R. L., Larsen P. R., Moore D. D. Thyroid hormone receptor binds to a site in the rat growth hormone promoter required for induction by thyroid hormone. Proc Natl Acad Sci U S A. 1987 Aug;84(16):5670–5674. doi: 10.1073/pnas.84.16.5670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Koenig R. J., Smith R. J. L6 cells as a tissue culture model for thyroid hormone effects on skeletal muscle metabolism. J Clin Invest. 1985 Aug;76(2):878–881. doi: 10.1172/JCI112046. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kolodny J. M., Larsen P. R., Silva J. E. In vitro 3,5,3'-triiodothyronine binding to rat cerebrocortical neuronal and glial nuclei suggests the presence of binding sites unavailable in vivo. Endocrinology. 1985 May;116(5):2019–2028. doi: 10.1210/endo-116-5-2019. [DOI] [PubMed] [Google Scholar]
  16. Larsen P. R., Harney J. W., Moore D. D. Repression mediates cell-type-specific expression of the rat growth hormone gene. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8283–8287. doi: 10.1073/pnas.83.21.8283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Larsen P. R., Harney J. W., Moore D. D. Sequences required for cell-type specific thyroid hormone regulation of rat growth hormone promoter activity. J Biol Chem. 1986 Nov 5;261(31):14373–14376. [PubMed] [Google Scholar]
  18. Mueckler M. M., Moran S., Pitot H. C. Transcriptional control of ornithine aminotransferase synthesis in rat kidney by estrogen and thyroid hormone. J Biol Chem. 1984 Feb 25;259(4):2302–2305. [PubMed] [Google Scholar]
  19. Narayan P., Towle H. C. Stabilization of a specific nuclear mRNA precursor by thyroid hormone. Mol Cell Biol. 1985 Oct;5(10):2642–2646. doi: 10.1128/mcb.5.10.2642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Pascual A., Casanova J., Samuels H. H. Photoaffinity labeling of thyroid hormone nuclear receptors in intact cells. J Biol Chem. 1982 Aug 25;257(16):9640–9647. [PubMed] [Google Scholar]
  21. Prost E., Moore D. D. CAT vectors for analysis of eukaryotic promoters and enhancers. Gene. 1986;45(1):107–111. doi: 10.1016/0378-1119(86)90138-1. [DOI] [PubMed] [Google Scholar]
  22. Sap J., Muñoz A., Damm K., Goldberg Y., Ghysdael J., Leutz A., Beug H., Vennström B. The c-erb-A protein is a high-affinity receptor for thyroid hormone. Nature. 1986 Dec 18;324(6098):635–640. doi: 10.1038/324635a0. [DOI] [PubMed] [Google Scholar]
  23. Schwartz H. L., Oppenheimer J. H. Nuclear triiodothyronine receptor sites in brain: probable identity with hepatic receptors and regional distribution. Endocrinology. 1978 Jul;103(1):267–273. doi: 10.1210/endo-103-1-267. [DOI] [PubMed] [Google Scholar]
  24. Selden R. F., Howie K. B., Rowe M. E., Goodman H. M., Moore D. D. Human growth hormone as a reporter gene in regulation studies employing transient gene expression. Mol Cell Biol. 1986 Sep;6(9):3173–3179. doi: 10.1128/mcb.6.9.3173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Shupnik M. A., Chin W. W., Habener J. F., Ridgway E. C. Transcriptional regulation of the thyrotropin subunit genes by thyroid hormone. J Biol Chem. 1985 Mar 10;260(5):2900–2903. [PubMed] [Google Scholar]
  26. Thompson C. C., Weinberger C., Lebo R., Evans R. M. Identification of a novel thyroid hormone receptor expressed in the mammalian central nervous system. Science. 1987 Sep 25;237(4822):1610–1614. doi: 10.1126/science.3629259. [DOI] [PubMed] [Google Scholar]
  27. Weinberger C., Thompson C. C., Ong E. S., Lebo R., Gruol D. J., Evans R. M. The c-erb-A gene encodes a thyroid hormone receptor. Nature. 1986 Dec 18;324(6098):641–646. doi: 10.1038/324641a0. [DOI] [PubMed] [Google Scholar]
  28. Yaffe B. M., Samuels H. H. Hormonal regulation of the growth hormone gene. Relationship of the rate of transcription to the level of nuclear thyroid hormone-receptor complexes. J Biol Chem. 1984 May 25;259(10):6284–6291. [PubMed] [Google Scholar]

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