Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/37340
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dc.contributor.authorBouzo-Lorenzo, M.-
dc.contributor.authorSanto-Zas, I.-
dc.contributor.authorLodeiro, M.-
dc.contributor.authorNogueiras, R.-
dc.contributor.authorCasanueva, F. F.-
dc.contributor.authorCastro, M.-
dc.contributor.authorPazos, Y.-
dc.contributor.authorTobin, Andrew B.-
dc.contributor.authorButcher, A. J.-
dc.contributor.authorCamiña, J. P.-
dc.date.accessioned2016-04-18T11:32:29Z-
dc.date.available2016-04-18T11:32:29Z-
dc.date.issued2016-03-03-
dc.identifier.citationScientific Reports, 2016, 6, p. 22495en
dc.identifier.urihttp://www.nature.com/articles/srep22495en
dc.identifier.urihttp://hdl.handle.net/2381/37340-
dc.description.abstractThe 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 Ser(362), Ser(363) and Thr(366) 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 Thr(350) and Ser(349) 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.en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pubmed/26935831-
dc.rightsCopyright © 2016, the authors. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en
dc.titleDistinct phosphorylation sites on the ghrelin receptor, GHSR1a, establish a code that determines the functions of ß-arrestinsen
dc.typeJournal Articleen
dc.identifier.doi10.1038/srep22495-
dc.identifier.eissn2045-2322-
dc.identifier.piisrep22495-
dc.description.statusPeer-revieweden
dc.description.versionPublisher Versionen
dc.type.subtypeJournal Article-
pubs.organisational-group/Organisationen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGYen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departmentsen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Molecular & Cell Biologyen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themesen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/Canceren
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/Molecular & Cellular Bioscienceen
pubs.organisational-group/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/Themes/Respiratory Scienceen
dc.dateaccepted2016-02-15-
Appears in Collections:Published Articles, MRC Toxicology Unit



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