Bouzo-Lorenzo, M., Santo-Zas, I., Lodeiro, M., Nogueiras, R., Casanueva, F. F., Castro, M., Pazos, Y., Tobin, A. B. , Butcher, A. J. and Camiña, J. P. (2016) Distinct phosphorylation sites on the ghrelin receptor, GHSR1a, establish a code that determines the functions of ß-arrestins. Scientific Reports, 6, p. 22495. (doi: 10.1038/srep22495) (PMID:26935831) (PMCID:PMC4776146)
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Abstract
The growth hormone secretagogue receptor, GHSR1a, mediates the biological activities of ghrelin, which includes the secretion of growth hormone, as well as the stimulation of appetite, food intake and maintenance of energy homeostasis. Mapping phosphorylation sites on GHSR1a and knowledge of how these sites control specific functional consequences unlocks new strategies for the development of therapeutic agents targeting individual functions. Herein, we have identified the phosphorylation of different sets of sites within GHSR1a which engender distinct functionality of ß-arrestins. More specifically, the Ser362, Ser363 and Thr366 residues at the carboxyl-terminal tail were primarily responsible for ß-arrestin 1 and 2 binding, internalization and ß-arrestin-mediated proliferation and adipogenesis. The Thr350 and Ser349 are not necessary for ß-arrestin recruitment, but are involved in the stabilization of the GHSR1a-ß-arrestin complex in a manner that determines the ultimate cellular consequences of ß-arrestin signaling. We further demonstrated that the mitogenic and adipogenic effect of ghrelin were mainly dependent on the ß-arrestin bound to the phosphorylated GHSR1a. In contrast, the ghrelin function on GH secretion was entirely mediated by G protein signaling. Our data is consistent with the hypothesis that the phosphorylation pattern on the C terminus of GHSR1a determines the signaling and physiological output.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Tobin, Andrew |
Authors: | Bouzo-Lorenzo, M., Santo-Zas, I., Lodeiro, M., Nogueiras, R., Casanueva, F. F., Castro, M., Pazos, Y., Tobin, A. B., Butcher, A. J., and Camiña, J. P. |
College/School: | College of Medical Veterinary and Life Sciences > School of Molecular Biosciences |
Journal Name: | Scientific Reports |
Publisher: | Nature Publishing Group |
ISSN: | 2045-2322 |
ISSN (Online): | 2045-2322 |
Copyright Holders: | Copyright © 2016 The Authors |
First Published: | First published in Scientific Reports 6:22495 |
Publisher Policy: | Reproduced under a Creative Commons License |
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