ArticleScience signaling2014
Nongenomic thyroid hormone signaling occurs through a plasma membrane-localized receptor.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
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- Photoinduced Inhibition of Neutrophil Extracellular Traps Formation by Dichromatic Light Irradiation.Current issues in molecular biology · 2025Article
- Advances and challenges in kidney fibrosis therapeutics.Nature reviews. Nephrology · 2025Review
- Metabolic Rewiring and Post-Translational Modifications: Unlocking the Mechanisms of Bone Turnover in Osteoporosis.Aging and disease · 2025Review
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- Thyroid Hormone Action by Genomic and Nongenomic Molecular Mechanisms.Methods in molecular biology (Clifton, N.J.) · 2025Article
- A plasma membrane-associated form of the androgen receptor enhances nuclear androgen signaling in osteoblasts and prostate cancer cells.Science signaling · 2024Article
- Review
- Protein Kinase G2 Is Essential for Skeletal Homeostasis and Adaptation to Mechanical Loading in Male but Not Female Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2023Article
- Thyroid hormone membrane receptor binding and transcriptional regulation in the sea urchinFrontiers in endocrinology · 2023Article
- TRα2-An Untuned Second Fiddle or Fine-Tuning Thyroid Hormone Action?International journal of molecular sciences · 2022Review
- 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
- Review
- µ-Crystallin: A thyroid hormone binding protein.Endocrine regulations · 2021Review
- Thyroid hormone: sex-dependent role in nervous system regulation and disease.Biology of sex differences · 2021Review
- Thyroxine Induces Acute Relaxation of Rat Skeletal Muscle Arteries via Integrin αvβ3, ERK1/2 and Integrin-Linked Kinase.Frontiers in physiology · 2021Article
- Diabetoporosis: Role of nitric oxide.EXCLI journal · 2021Review
- RNA-activated protein kinase differentially modulates innate immune response mediated by supraphysiological concentrations of thyroid hormone.Innate immunity · 2020Article
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Thyroid hormone (TH) is essential for vertebrate development and the homeostasis of most adult tissues, including bone. TH stimulates target gene expression through the nuclear thyroid receptors TRα and TRβ; however, TH also has rapid, transcription-independent (nongenomic) effects. We found a previously uncharacterized plasma membrane-bound receptor that was necessary and sufficient for nongenomic TH signaling in several cell types. We determined that this receptor is generated by translation initiation from an internal methionine of TRα, which produces a transcriptionally incompetent protein that is palmitoylated and associates with caveolin-containing plasma membrane domains. TH signaling through this receptor stimulated a pro-proliferative and pro-survival program by increasing the intracellular concentrations of calcium, nitric oxide (NO), and cyclic guanosine monophosphate (cGMP), which led to the sequential activation of protein kinase G II (PKGII), the tyrosine kinase Src, and extracellular signal-regulated kinase (ERK) and Akt signaling. Hypothyroid mice exhibited a cGMP-deficient state with impaired bone formation and increased apoptosis of osteocytes, which was rescued by a direct stimulator of guanylate cyclase. Our results link nongenomic TH signaling to a previously uncharacterized membrane-bound receptor, and identify NO synthase, guanylate cyclase, and PKGII as TH effectors that activate kinase cascades to regulate cell survival and proliferation.
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Registered trials
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.