ArticleMolecular and cellular biology1995
Functional regulation of thyroid hormone receptor variant TR alpha 2 by phosphorylation.
Article in Molecular and cellular biology, 1995. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 76 citations in OpenAlex.
- RNA Sequencing Reveals a Strong Predominance ofInternational journal of molecular sciences · 2024Article
- TRα2-An Untuned Second Fiddle or Fine-Tuning Thyroid Hormone Action?International journal of molecular sciences · 2022Review
- Thyroid hormone receptor phosphorylation regulates acute fasting-induced suppression of the hypothalamic-pituitary-thyroid axis.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A Direct Comparison of Thyroid Hormone Receptor Protein Levels in Mice Provides Unexpected Insights into Thyroid Hormone Action.Thyroid : official journal of the American Thyroid Association · 2020Article
- New insights on thyroid hormone mediated regulation of herpesvirus infections.Cell & bioscience · 2017Review
- Resistance to thyroid hormone caused by a mutation in thyroid hormone receptor (TR)α1 and TRα2: clinical, biochemical, and genetic analyses of three related patients.The lancet. Diabetes & endocrinology · 2014Article
- Excess folate during adolescence suppresses thyroid function with permanent deficits in motivation and spatial memory.Genes, brain, and behavior · 2012Article
- Structure and expression of two nuclear receptor genes in marsupials: insights into the evolution of the antisense overlap between the α-thyroid hormone receptor and Rev-erbα.BMC molecular biology · 2010Article
- Ontogenetic profile of the expression of thyroid hormone receptors in rat and human corpora cavernosa of the penis.The journal of sexual medicine · 2010Article
- Modulating nuclear receptor function: may the phos be with you.The Journal of clinical investigation · 1999Review
- Mice devoid of all known thyroid hormone receptors are viable but exhibit disorders of the pituitary-thyroid axis, growth, and bone maturation.Genes & development · 1999Article
- Screening methods for thyroid hormone disruptors.Environmental health perspectives · 1999Review
- Abnormal heart rate and body temperature in mice lacking thyroid hormone receptor alpha 1.The EMBO journal · 1998Article
- Phosphorylation of serine-167 on the human oestrogen receptor is important for oestrogen response element binding and transcriptional activation.The Biochemical journal · 1997Article
- Protein kinase A-dependent phosphorylation modulates DNA-binding activity of hepatocyte nuclear factor 4.Molecular and cellular biology · 1997Article
- Steroid hormone receptors and their regulation by phosphorylation.The Biochemical journal · 1996Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The thyroid hormone (T3) receptor (TR) variant TR alpha 2 is abundant in brain but does not bind T3 because of its unique C terminus. The only known function of TR alpha 2, inhibition of TR-dependent transactivation, involves competition for T3 response elements. Paradoxically, in vitro-translated TR alpha 2 bound poorly to these sites. We report here that dephosphorylation of TR alpha 2 restored its DNA binding. Mutation of C-terminal serine residues to alanine (TR alpha 2-SA) was equally effective. The C terminus of TR alpha 2 was phosphorylated in a human cell line, whereas that of TR alpha 2-SA was not. Conversely, TR alpha 2-SA was a much better inhibitor of T3 action than was wild-type TR alpha 2. The dominant negative activity of TR alpha 2-SA was less than stoichiometric with TR concentration, possibly because it was unable to heterodimerize with retinoid X receptor, which enhances the binding of other TRs. Purified casein kinase II as well as a reticulocyte casein kinase II-like activity phosphorylated TR alpha 2 on serines 474 and 475. Mutation of these two residues to alanine was sufficient to restore DNA binding. Thus, DNA binding by TR alpha 2 is regulated by phosphorylation at a site distant from the DNA-binding domain. The increased dominant negative activity of a nonphosphorylatable form of TR alpha 2 suggests that phosphorylation may provide a rapid, T3-independent mechanism for cell-specific modulation of the expression of T3-responsive genes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.