RT Journal Article
T1 Distinct phosphorylation sites on the ghrelin receptor, GHSR1a, establish a code that determines the functions of ß-arrestins.
A1 Bouzo Lorenzo, Mónica
A1 Santo Zas, Icía
A1 Lodeiro, Maria
A1 Nogueiras Pozo, Rubén
A1 Casanueva Freijo, Felipe
A1 Castro Pérez, María de los Ángeles
A1 Pazos Randulfe, Yolanda
A1 Tobin, Andrew
A1 Butcher, Adrian
A1 Pérez Camiña, Jesús
K1 Cell biology
K1 Endocrinology
AB 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 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
PB Nature Publishing Group
YR 2016
FD 2016-03-03
LK http://hdl.handle.net/10347/15909
UL http://hdl.handle.net/10347/15909
LA eng
NO Bouzo-Lorenzo, M.  et al.  Distinct phosphorylation sites on the ghrelin receptor, GHSR1a, establish a code that determines the functions of ß-arrestins.  Sci. Rep. 6 , 22495; doi: 10.1038/ srep22495 (2016)
NO This work was supported by grants from Instituto de Salud Carlos III (ISCIII; PI15/01537 and PI12/02388) and FEDER Funds (MINECO, Spain). The work of JP Camina and Y Pazos are funded by the SERGAS through a research-staff stabilization contract. Andrew Tobin and Adrian Butcher are supported by an MRC Toxicology Unit program grant. ISCIII funds M Bouzo-Lorenzo through a pre-doctorate research scholarship
DS Minerva
RD 24 abr 2026