The search result changed since you submitted your search request. Documents might be displayed in a different sort order.
  • search hit 1 of 396
Back to Result List

Proteolytic cleavage of the extracellular domain affects signaling of parathyroid hormone 1 receptor

Please always quote using this 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.show moreshow less

Download full text files

Export metadata

Additional Services

Share in Twitter Search Google Scholar Statistics
Metadaten
Author: Christoph Klenk, Leif Hommers, Martin J. Lohse
URN:urn:nbn:de:bvb:20-opus-262055
Document Type:Journal article
Faculties: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
Language:English
Parent Title (English):Frontiers in Endocrinology
ISSN:1664-2392
Year of Completion:2022
Volume:13
Article Number:839351
Source:Frontiers in Endocrinology (2022) 13:839351. doi:10.3389/fendo.2022.839351
DOI:https://doi.org/10.3389/fendo.2022.839351
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:GPCRs; biased signaling; ectodomain cleavage; matrix metalloproteinase; parathyroid hormone 1 receptor
Release Date:2023/01/30
Date of first Publication:2022/02/22
EU-Project number / Contract (GA) number:232944
OpenAIRE:OpenAIRE
Open-Access-Publikationsfonds / Förderzeitraum 2022
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International