Constitutive activation of the thyrotropin receptor by deletion of a portion of the extracellular domain
| Autor: | Mei-Luo Zhang, Hideo Sugawa, Shinji Kosugi, Tomohiko Mori |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
endocrine system
endocrine system diseases B-cell receptor Biophysics Thyrotropin Biology Kidney Transfection Biochemistry Thyrotropin receptor Cell Line Thyrotropin-releasing hormone receptor Chlorocebus aethiops Enzyme-linked receptor Cyclic AMP Animals Humans 5-HT5A receptor Receptor Molecular Biology Sequence Deletion Cell Membrane Receptors Thyrotropin Cell Biology Recombinant Proteins Cell biology Rats Transmembrane domain Kinetics Interleukin-21 receptor Cancer research hormones hormone substitutes and hormone antagonists |
| Zdroj: | Biochemical and biophysical research communications. 211(1) |
| ISSN: | 0006-291X |
| Popis: | Mutations involving the transmembrane domain of the thyrotropin receptor (TSHR) confer constitutive activation of the receptor and can cause human diseases. Naturally occurring activating mutations identified to date are located only in the transmembrane domain of the receptor. We now report a mutant involving the extracellular domain of the TSHR which also shows constitutive activation. This mutation is missing residues 339-367 located in the C-terminal portion of the extracellular domain. When expressed in COS-7 cells, the mutated TSHR (M3B) retained similar TSH binding ability to that of the wild-type receptor. However, the basal cAMP production without TSH stimulation in COS-7 cells transfected with M3B cDNA was significantly higher than that of COS-7 cells with wild-type receptor, indicating that the mutant receptor is constitutively activated. Our results provide new insight into the mechanism of receptor activation. |
| Databáze: | OpenAIRE |
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