Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2002 Jul;110(2):161-4.
doi: 10.1172/JCI16234.

The TSH receptor reveals itself

Terry Davies  1 , Russell Marians, Rauf Latif
Affiliations
Review

The TSH receptor reveals itself

Terry Davies et al. J Clin Invest. 2002 Jul.
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Two possible structural configurations of TSH receptor. (a) The uncleaved receptor is shown with a “buried” structure. The ectodomain and transmembrane interactions result in a “closed” conformation (connecting dotted lines). (b) Cleavage may induce an “open” conformation, a step that is thought to be a precondition for subsequent changes in receptor localization and activity, as described in the text and shown in Figure 2. This figure is adapted from ref. with permission.
Figure 2
Figure 2
A model for oligomerization in TSH receptor signaling. (a) TSH receptors initially exist in an open conformation as cleaved oligomers residing on the cell surface outside lipid rafts. Signal-transducing Gs proteins, on the other hand, are restricted to lipid rafts. (b) Following TSH binding, the oligomers break apart into monomers. Conversely, stimulating antibodies, as found in sera from patients with the autoimmune disorder Graves disease, are proposed to favor formation of TSH receptor dimers; blocking antibodies, are unable to bring about this conformational change. (c) Dissociated monomers, as well as dimers, move into the lipid rafts and bind to Gs proteins, thereby initiating the signaling cascade. In the case of TSH, the signal is rapid and brief because of faster movement of monomers into the lipid rafts, in contrast to the retarded movement of the dimers. Multivalent blocking TSHR antibodies may cross-link the oligomers, thereby preventing them from dissociating and impeding their entry into lipid rafts.
See this image and copyright information in PMC

Comment on

References

    1. Davies, T.F. 2000. Werner & Ingbar’s the thyroid: a fundamental and clinical text. Lippincott Williams & Wilkins. Philadelphia, Pennsylvania, USA. 518–530.
    1. Parmentier M, et al. Molecular cloning of the thyrotropin receptor. Science. 1989;246:1620–1622. - PubMed
    1. Misrahi M, et al. Cloning, sequencing and expression of human TSH receptor. Biochem Biophys Res Commun. 1990;166:394–403. - PubMed
    1. Nagayama Y, Kaufman KD, Seto P, Rapoport B. Molecular cloning, sequence and functional expression of the cDNA for the human thyrotropin receptor. Biochem Biophys Res Commun. 1989;165:1184–1190. - PubMed
    1. Gross B, Misrahi M, Sar S, Milgrom E. Composite structure of the human thyrotropin receptor gene. Biochem Biophys Res Commun. 1991;177:679–687. - PubMed