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Mol Biol Cell. 2019 Oct 10:mbcE19060326. doi: 10.1091/mbc.E19-06-0326. [Epub ahead of print]

Signaling of ghrelin at GHSR1b and OX1R receptor heterodimers.

Author information

1
Department of Endocrinology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, China.
2
Outpatient Service Center, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, 264000, China.
3
Department of Health Care for Cadres,The Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical, Yantai, Shandong, 264000, China.
4
Institute of Immunology,Icahn School of Medicine at Mount Sinai,New York,NY 10029,USA.
5
Basic Medical School, Jining Medical University, Shandong, 272067, China.

Abstract

Growth hormone receptor 1b (GHSR1b) and orexin type 1 receptor (OX1R) have many similar characteristics in terms of their functions and body distribution and are involved in various physiological functions. In this study, we explored the possibility of GHSR1b and OX1R dimerization. Bioluminescence (BRET), fluorescence resonance energy transfer (FRET) and coimmunoprecipitation (Co-IP) were used to analyse the formation of GHSR1b and OX1R heteromers in cells. We also explored their signal transduction pathway mechanism. The results showed that ghrelin could stimulate GHSR1b/OX1R heterodimer cellsto increase Gαs protein activation and induce downstream signalling pathway activity. GHSR1b/OX1R heteromers triggered ghrelin-induced Gαs/protein kinase A signalling pathway activity. Thus, GHSR1b can form a heterodimer with OX1R, leading to increased protein kinase A activity. At the same time, stimulation with orexinA did not alter G protein-coupled receptor (GPCR) interactions with Gα protein subunits. Moreover, ghrelin induced a significant increase in cell proliferation. These results suggest that heterodimers of ghrelin and GHSR1b/OX1R promote the upregulation of a Gαs-cAMP-cAMP-responsive element signalling pathway. The nature of this signalling pathway may have significant implications in regulating physiological functions.

PMID:
31599699
DOI:
10.1091/mbc.E19-06-0326

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