The human thyrotropin receptor activates G-proteins gs and Gq/11
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The human thyrotropin receptor leads upon activation to the stimulation of phospholipase C and adenylyl cyclase. It is presently not known whether this bifurcating signaling occurs via two different G-proteins (Gq/11 and Gs) or via one G-protein (Gs). Receptor-activated Gs releases beta gamma subunits and alpha s, which then could regulate phospholipase C and adenylyl cyclase, respectively. In order to elucidate the signaling pathways induced by the activated thyroid-stimulating hormone (TSH) receptor, we studied the coupling of the TSH receptor to Gs and Gq/11 in human thyroid membranes. TSH concentration dependently led to the activation of two forms of Gs (Gs short and Gs long) as well as of Gq and G11, demonstrating that signaling pathways induced by TSH already bifurcate in the course of the receptor-G-protein interaction. These data strongly suggest the concept that phospholipase C and adenylyl cyclase activation through the TSH receptor are mediated by Gq/11 and Gs, respectively.
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TSH can differentially activate Gαs and Gαq/11 in a concentration-dependent manner.
“TSH can differentially activate Gαs and Gαq/11 in a concentration-dependent manner (116).”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [116]
Cites
Type-Specific Regulation of Adenylyl Cyclase by G Protein βγ Subunits
Tang, W.-J., & Gilman, A. G. (1991) · Science · doi:10.1126/science.1962211 · Cited by 1,091 · see citing works
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Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion
Jing, L., & Zhang, Q. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.992883 · Cited by 61 · see citing works
- Authors
- Allgeier, A., Offermanns, S., Van Sande, J., Spicher, K., Schultz, G., & Dumont, J. E.
- Affiliations
- California Institute of Technology (US)
- ORCID
- Offermanns, S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1994-05
- Volume
- 269
- Issue
- 19
- Pages
- 13733-13735
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1617916547
- Cited by
- 192
- References
- 1
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 5 · 2017: 4 · 2016: 6 · 2015: 5 · 2014: 5 · 2013: 5 · 2012: 2
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Keywords
- TSH receptor, Gs protein, Gαq/11, G11, G protein coupling, phospholipase C, adenylate cyclase, beta gamma subunits, thyroid membranes, thyroid-stimulating hormone
- MeSH terms
- Adenylyl Cyclases, Amino Acid Sequence, Animals, Enzyme Activation, Humans, Membranes, Molecular Sequence Data, Type C Phospholipases, Precipitin Tests, Receptors, Thyrotropin, Thyroid Gland, GTP-Binding Proteins, In Vitro Techniques
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