ArticleEndocrinology2014
A rapid cytoplasmic mechanism for PI3 kinase regulation by the nuclear thyroid hormone receptor, TRβ, and genetic evidence for its role in the maturation of mouse hippocampal synapses in vivo.
Article in Endocrinology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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49 citing papers in PubMed, 92 citations in OpenAlex.
- Transcriptional Cofactors for Thyroid Hormone Receptors.Endocrinology · 2025Review
- Evidence for thyroid hormone regulation of amygdala-dependent fear-relevant memory and plasticity.Molecular psychiatry · 2025Article
- Targeting THR-β for MASLD: Mechanisms and Drug Development.Drug design, development and therapy · 2025Review
- Thyroid Hormone Action by Genomic and Nongenomic Molecular Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Targeting Androgen, Thyroid Hormone, and Vitamin A and D Receptors to Treat Prostate Cancer.International journal of molecular sciences · 2024Review
- Sex-Specific Effects of THRβ Signaling on Metabolic Responses to High Fat Diet in Mice.Endocrinology · 2024Article
- Thyroid hormone membrane receptor binding and transcriptional regulation in the sea urchinFrontiers in endocrinology · 2023Article
- Thyroid hormone-induced cell death in sea urchin metamorphic development.The Journal of experimental biology · 2022Article
- Cardioprotection by Hypothyroidism Is Not Mediated by Favorable Hemodynamics-Role of Canonical Thyroid Hormone Receptor Alpha Signaling.International journal of molecular sciences · 2022Article
- TRα2-An Untuned Second Fiddle or Fine-Tuning Thyroid Hormone Action?International journal of molecular sciences · 2022Review
- Histological, functional and transcriptomic alterations in the juvenile hippocampus in a mouse model of thyroid hormone resistance.European thyroid journal · 2022Article
- The interplay of thyroid hormones and the immune system - where we stand and why we need to know about it.European journal of endocrinology · 2022Review
- Subcellular Distribution of Thyroid Hormone Receptor Beta in Ovarian Cancer.International journal of molecular sciences · 2022Article
- Recognition of fold- and function-specific sites in the ligand-binding domain of the thyroid hormone receptor-like family.Frontiers in endocrinology · 2022Article
- Thyroid hormone receptor alpha sumoylation modulates white adipose tissue stores.Scientific reports · 2021Article
- The Nutritional Supply of Iodine and Selenium Affects Thyroid Hormone Axis Related Endpoints in Mice.Nutrients · 2021Article
- Article
- Thyroid hormone receptor β sumoylation is required for thyrotropin regulation and thyroid hormone production.JCI insight · 2021Article
- Thyroid Hormone Receptor Beta Inhibits PI3K-Akt-mTOR Signaling Axis in Anaplastic Thyroid Cancer via Genomic Mechanisms.Journal of the Endocrine Society · 2021Article
- Selective Inhibition of Genomic and Non-Genomic Effects of Thyroid Hormone Regulates Muscle Cell Differentiation and Metabolic Behavior.International journal of molecular sciences · 2021Article
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10 authors at 4 institutions in 1 country.
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Abstract
Several rapid physiological effects of thyroid hormone on mammalian cells in vitro have been shown to be mediated by the phosphatidylinositol 3-kinase (PI3K), but the molecular mechanism of PI3K regulation by nuclear zinc finger receptor proteins for thyroid hormone and its relevance to brain development in vivo have not been elucidated. Here we show that, in the absence of hormone, the thyroid hormone receptor TRβ forms a cytoplasmic complex with the p85 subunit of PI3K and the Src family tyrosine kinase, Lyn, which depends on two canonical phosphotyrosine motifs in the second zinc finger of TRβ that are not conserved in TRα. When hormone is added, TRβ dissociates and moves to the nucleus, and phosphatidylinositol (3, 4, 5)-trisphosphate production goes up rapidly. Mutating either tyrosine to a phenylalanine prevents rapid signaling through PI3K but does not prevent the hormone-dependent transcription of genes with a thyroid hormone response element. When the rapid signaling mechanism was blocked chronically throughout development in mice by a targeted point mutation in both alleles of Thrb, circulating hormone levels, TRβ expression, and direct gene regulation by TRβ in the pituitary and liver were all unaffected. However, the mutation significantly impaired maturation and plasticity of the Schaffer collateral synapses on CA1 pyramidal neurons in the postnatal hippocampus. Thus, phosphotyrosine-dependent association of TRβ with PI3K provides a potential mechanism for integrating regulation of development and metabolism by thyroid hormone and receptor tyrosine kinases.
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