Abstract
A cDNA encoding a specific form of thyroid hormone receptor expressed in human liver, kidney, placenta, and brain was isolated from a human kidney library. Identical clones were found in human placenta and HepG2 cDNA libraries. The cDNA encodes a 490-amino acid protein (Mr, 54,824). When expressed and translated in vitro, the protein product binds triiodothyronine with Ka of 2.3 X 10(9) M-1. This protein, designated human thyroid hormone receptor type alpha 2 (hTR alpha 2), has the same domain structure as other members of the v-erbA-related superfamily of receptor genes. It is similar to thyroid hormone receptor type alpha described in chicken and rat and less similar to human thyroid hormone receptor type beta (formerly referred to as c-erbA beta) from placenta. However, it is distinguished from these receptors by an extension of the C-terminal hormone binding domain making it 80 amino acids longer than rat thyroid hormone receptor type alpha 1 [Thompson, C.C., Weinberger, C., Lebo, R. & Evans, R. M. (1987) Science 237, 1610-1614]. Different sizes of mRNA found in liver (2.5 kilobases) and kidney (2 kilobases) suggest there may be tissue-specific processing of the primary transcript of this gene. Identification of human thyroid hormone receptor type alpha 2 indicates that two or more forms of thyroid hormone receptor exist in human tissues and may explain the normal variation in thyroid hormone responsiveness of various organs and the selective tissue abnormalities found in the thyroid hormone resistance syndromes.
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.
- Arriza J. L., Weinberger C., Cerelli G., Glaser T. M., Handelin B. L., Housman D. E., Evans R. M. Cloning of human mineralocorticoid receptor complementary DNA: structural and functional kinship with the glucocorticoid receptor. Science. 1987 Jul 17;237(4812):268–275. doi: 10.1126/science.3037703. [DOI] [PubMed] [Google Scholar]
- Bell G. I., Fong N. M., Stempien M. M., Wormsted M. A., Caput D., Ku L. L., Urdea M. S., Rall L. B., Sanchez-Pescador R. Human epidermal growth factor precursor: cDNA sequence, expression in vitro and gene organization. Nucleic Acids Res. 1986 Nov 11;14(21):8427–8446. doi: 10.1093/nar/14.21.8427. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Bernal J., Refetoff S., DeGroot L. J. Abnormalities of triiodothyronine binding to lymphocyte and fibroblast nuclei from a patient with peripheral tissue resistance to thyroid hormone action. J Clin Endocrinol Metab. 1978 Dec;47(6):1266–1272. doi: 10.1210/jcem-47-6-1266. [DOI] [PubMed] [Google Scholar]
- Catanzaro D. F., West B. L., Baxter J. D., Reudelhuber T. L. A pituitary-specific factor interacts with an upstream promotor element in the rat growth hormone gene. Mol Endocrinol. 1987 Jan;1(1):90–96. doi: 10.1210/mend-1-1-90. [DOI] [PubMed] [Google Scholar]
- 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]
- Green S., Chambon P. A superfamily of potentially oncogenic hormone receptors. Nature. 1986 Dec 18;324(6098):615–617. doi: 10.1038/324615a0. [DOI] [PubMed] [Google Scholar]
- Gustafson T. A., Markham B. E., Bahl J. J., Morkin E. Thyroid hormone regulates expression of a transfected alpha-myosin heavy-chain fusion gene in fetal heart cells. Proc Natl Acad Sci U S A. 1987 May;84(10):3122–3126. doi: 10.1073/pnas.84.10.3122. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ichikawa K., DeGroot L. J. Purification and characterization of rat liver nuclear thyroid hormone receptors. Proc Natl Acad Sci U S A. 1987 May;84(10):3420–3424. doi: 10.1073/pnas.84.10.3420. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ichikawa K., Hughes I. A., Horwitz A. L., DeGroot L. J. Characterization of nuclear thyroid hormone receptors of cultured skin fibroblasts from patients with resistance to thyroid hormone. Metabolism. 1987 Apr;36(4):392–399. doi: 10.1016/0026-0495(87)90214-9. [DOI] [PubMed] [Google Scholar]
- Krieg P. A., Melton D. A. Functional messenger RNAs are produced by SP6 in vitro transcription of cloned cDNAs. Nucleic Acids Res. 1984 Sep 25;12(18):7057–7070. doi: 10.1093/nar/12.18.7057. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Oppenheimer J. H. Thyroid hormone action at the nuclear level. Ann Intern Med. 1985 Mar;102(3):374–384. doi: 10.7326/0003-4819-102-3-374. [DOI] [PubMed] [Google Scholar]
- 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]
- Refetoff S., DeGroot L. J., Benard B., DeWind L. T. Studies of a sibship with apparent hereditary resistance to the intracellular action of thyroid hormone. Metabolism. 1972 Aug;21(8):723–756. doi: 10.1016/0026-0495(72)90121-7. [DOI] [PubMed] [Google Scholar]
- Sanger F., Coulson A. R., Barrell B. G., Smith A. J., Roe B. A. Cloning in single-stranded bacteriophage as an aid to rapid DNA sequencing. J Mol Biol. 1980 Oct 25;143(2):161–178. doi: 10.1016/0022-2836(80)90196-5. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Torresani J., DeGroot L. J. Triiodothyronine binding to liver nuclear solubilized proteins in vitro. Endocrinology. 1975 May;96(5):1201–1209. doi: 10.1210/endo-96-5-1201. [DOI] [PubMed] [Google Scholar]
- Ullrich A., Shine J., Chirgwin J., Pictet R., Tischer E., Rutter W. J., Goodman H. M. Rat insulin genes: construction of plasmids containing the coding sequences. Science. 1977 Jun 17;196(4296):1313–1319. doi: 10.1126/science.325648. [DOI] [PubMed] [Google Scholar]
- 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]
- Ye Z. S., Samuels H. H. Cell- and sequence-specific binding of nuclear proteins to 5'-flanking DNA of the rat growth hormone gene. J Biol Chem. 1987 May 5;262(13):6313–6317. [PubMed] [Google Scholar]