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

文献类型：期刊论文

作者Shao, Lijun1,2,3,4; Chen, Yan5; Zhang, Shikai6; Zhang, Zhihui6; Cao, Yongbing6; Yang, Dehua1,2,3,4; Wang, Ming-Wei1,2,3,4,5,7
刊名ACTA PHARMACEUTICA SINICA B
出版日期2022-02-01
卷号12期号:2页码:637-650
关键词G protein-coupled receptor Glucagon receptor family Receptor activity-modulating protein Signaling Allosteric modulation GPCR-RAMP interaction Receptor pharmacology Ligand selectivity
ISSN号2211-3835
DOI10.1016/j.apsb.2021.07.028
通讯作者Yang, Dehua(dhyang@simm.ac.cn) ; Wang, Ming-Wei(mwwang@simm.ac.cn)
英文摘要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/).
WOS关键词ACTIVITY-MODIFYING PROTEINS ; EXTRACELLULAR DOMAIN ; AMYLIN RECEPTORS ; ADRENOMEDULLIN ; PHARMACOLOGY ; OXYNTOMODULIN ; ACTIVATION ; EXPRESSION
资助项目National Key R&D Programs of China[2018YFA0507000] ; National Science Foundation of China[81773792] ; National Science Foundation of China[81973373] ; National Science Foundation of China[81872915] ; National Science Foundation of China[82073904] ; National Science and Technology Major Project of China-Key New Drug Creation and Manufacturing Program[2018ZX09735-001] ; National Science and Technology Major Project of China-Key New Drug Creation and Manufacturing Program[2018ZX09711002-002-005] ; Novo Nordisk-CAS Research Fund[NNCAS-2017-1CC]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000760951600009
出版者INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
源URL[http://119.78.100.183/handle/2S10ELR8/300209]  
专题中国科学院上海药物研究所
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
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):637-650.
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),637-650.
MLA Shao, Lijun,et al."Modulating effects of RAMPs on signaling profiles of the glucagon receptor family".ACTA PHARMACEUTICA SINICA B 12.2(2022):637-650.

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来源：上海药物研究所

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