Proteolytic cleavage of the extracellular domain affects signaling of parathyroid hormone 1 receptor
Zitieren Sie bitte immer diese URN: urn:nbn:de:bvb:20-opus-262055
- Parathyroid hormone 1 receptor (PTH1R) is a member of the class B family of G protein-coupled receptors, which are characterized by a large extracellular domain required for ligand binding. We have previously shown that the extracellular domain of PTH1R is subject to metalloproteinase cleavage in vivo that is regulated by ligand-induced receptor trafficking and leads to impaired stability of PTH1R. In this work, we localize the cleavage site in the first loop of the extracellular domain using amino-terminal protein sequencing of purifiedParathyroid hormone 1 receptor (PTH1R) is a member of the class B family of G protein-coupled receptors, which are characterized by a large extracellular domain required for ligand binding. We have previously shown that the extracellular domain of PTH1R is subject to metalloproteinase cleavage in vivo that is regulated by ligand-induced receptor trafficking and leads to impaired stability of PTH1R. In this work, we localize the cleavage site in the first loop of the extracellular domain using amino-terminal protein sequencing of purified receptor and by mutagenesis studies. We further show, that a receptor mutant not susceptible to proteolytic cleavage exhibits reduced signaling to G\(_s\) and increased activation of G\(_q\) compared to wild-type PTH1R. These findings indicate that the extracellular domain modulates PTH1R signaling specificity, and that its cleavage affects receptor signaling.…
Autor(en): | Christoph Klenk, Leif Hommers, Martin J. Lohse |
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URN: | urn:nbn:de:bvb:20-opus-262055 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Institut für Pharmakologie und Toxikologie |
Medizinische Fakultät / Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie | |
Fakultät für Biologie / Rudolf-Virchow-Zentrum | |
Medizinische Fakultät / Comprehensive Cancer Center Mainfranken | |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Frontiers in Endocrinology |
ISSN: | 1664-2392 |
Erscheinungsjahr: | 2022 |
Band / Jahrgang: | 13 |
Aufsatznummer: | 839351 |
Originalveröffentlichung / Quelle: | Frontiers in Endocrinology (2022) 13:839351. doi:10.3389/fendo.2022.839351 |
DOI: | https://doi.org/10.3389/fendo.2022.839351 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | GPCRs; biased signaling; ectodomain cleavage; matrix metalloproteinase; parathyroid hormone 1 receptor |
Datum der Freischaltung: | 30.01.2023 |
Datum der Erstveröffentlichung: | 22.02.2022 |
EU-Projektnummer / Contract (GA) number: | 232944 |
OpenAIRE: | OpenAIRE |
Open-Access-Publikationsfonds / Förderzeitraum 2022 | |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |