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| Item Type: | Preprint | ||||
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| Title: | Proteolytic cleavage of the extracellular domain affects signaling of parathyroid hormone receptor 1 | ||||
| Creators Name: | Klenk, C. and Hommers, L. and Lohse, M.J. | ||||
| Abstract: | 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 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. | ||||
| Source: | bioRxiv | ||||
| Publisher: | Cold Spring Harbor Laboratory Press | ||||
| Article Number: | 2021.12.16.472984 | ||||
| Date: | 19 January 2022 | ||||
| Official Publication: | https://doi.org/10.1101/2021.12.16.472984 | ||||
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