Modulating effects of RAMPs on signaling profiles of the glucagon receptor family

doi:10.1016/j.apsb.2021.07.028

	Modulating effects of RAMPs on signaling profiles of the glucagon receptor family
	Shao, Lijun1,2,3,4 ; Chen, Yan 5; Zhang, Shikai 6; Zhang, Zhihui 6; Cao, Yongbing 6; Yang, Dehua 1,2,3,4; Wang, Ming-Wei1,2,3,4,5,7
	2022-02
发表期刊	ACTA PHARMACEUTICA SINICA B (IF:14.7[JCR-2023],14.1[5-Year])
ISSN	2211-3835
EISSN	2211-3843
卷号	12 期号:2
发表状态	已发表
DOI	10.1016/j.apsb.2021.07.028
摘要	Receptor activity-modulating proteins (RAMPs) are accessory molecules that form complexes with specific G protein-coupled receptors (GPCRs) and modulate their functions. It is established that RAMP interacts with the glucagon receptor family of GPCRs but the underlying mechanism is poorly understood. In this study, we used a bioluminescence resonance energy transfer (BRET) approach to comprehensively investigate such interactions. In conjunction with cAMP accumulation, Gaq activation and b-arrestin1/2 recruitment assays, we not only verified the GPCR-RAMP pairs previously reported, but also identified new patterns of GPCR-RAMP interaction. While RAMP1 was able to modify the three signaling events elicited by both glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), and RAMP2 mainly affected b-arrestin1/2 recruitment by GCGR, GLP-1R and glucagon-like peptide-2 receptor, RAMP3 showed a widespread negative impact on all the family members except for growth hormone-releasing hormone receptor covering the three pathways. Our results suggest that RAMP modulates both G protein dependent and independent signal transduction among the glucagon receptor family members in a receptor-specific manner. Mapping such interactions provides new insights into the role of RAMP in ligand recognition and receptor activation. (c) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
关键词	G protein-coupled receptor Glucagon receptor family Receptor activity-modulating protein Signaling Allosteric modulation GPCR-RAMP interaction Receptor pharmacology Ligand selectivity
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收录类别	SCI ; SCIE
语种	英语
资助项目	National Key R&D Programs of China[2018YFA0507000] ; National Science Foundation of China[81773792,81973373,81872915,82073904] ; National Science and Technology Major Project of China-Key New Drug Creation and Manufacturing Program["2018ZX09735-001","2018ZX09711002-002-005"] ; Novo Nordisk-CAS Research Fund[NNCAS-2017-1CC]
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Pharmacology & Pharmacy
WOS记录号	WOS:000760951600009
出版者	INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/162936
专题	生命科学与技术学院_博士生生命科学与技术学院_特聘教授组_王明伟组
通讯作者	Yang, Dehua; Wang, Ming-Wei
作者单位	1.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, CAS Key Lab Receptor Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China 6.Shanghai Univ Tradit Chinese Med, Shanghai TCM Integrated Hosp, Shanghai 200082, Peoples R China 7.Fudan Univ, Sch Basic Med Sci, Dept Pharmacol, Shanghai 200032, Peoples R China
第一作者单位	生命科学与技术学院
通讯作者单位	生命科学与技术学院
推荐引用方式 GB/T 7714	Shao, Lijun,Chen, Yan,Zhang, Shikai,et al. Modulating effects of RAMPs on signaling profiles of the glucagon receptor family[J]. ACTA PHARMACEUTICA SINICA B,2022,12(2).
APA	Shao, Lijun.,Chen, Yan.,Zhang, Shikai.,Zhang, Zhihui.,Cao, Yongbing.,...&Wang, Ming-Wei.(2022).Modulating effects of RAMPs on signaling profiles of the glucagon receptor family.ACTA PHARMACEUTICA SINICA B,12(2).
MLA	Shao, Lijun,et al."Modulating effects of RAMPs on signaling profiles of the glucagon receptor family".ACTA PHARMACEUTICA SINICA B 12.2(2022).