中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 新药研究国家重点实验室
Constitutive signal bias mediated by the human GHRHR splice variant 1

文献类型：期刊论文

作者Cong, Zhaotong1,2; Zhou, Fulai3; Zhang, Chao4,5; Zou, Xinyu6; Zhang, Huibing7; Wang, Yuzhe5,8; Zhou, Qingtong1; Cai, Xiaoqing3,8; Liu, Qiaofeng2; Li, Jie1
刊名PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
出版日期2021-10-05
卷号118期号:40页码:10
关键词class B1 GPCR receptor bias cancer cell proliferation
ISSN号0027-8424
DOI10.1073/pnas.2106606118
通讯作者Xu, H. Eric(eric.xu@simm.ac.cn) ; Cheng, Xi(xicheng@simm.ac.cn) ; Yang, Dehua(dhyang@simm.ac.cn) ; Wang, Ming-Wei(mwwang@simm.ac.cn)
英文摘要Alternative splicing of G protein-coupled receptors has been observed, but their functions are largely unknown. Here, we report that a splice variant (SV1) of the human growth hormone-releasing hormone receptor (GHRHR) is capable of transducing biased signal. Differing only at the receptor N terminus, GHRHR predominantly activates Gs while SV1 selectively couples to beta-arrestins. Based on the cryogenic electron microscopy structures of SV1 in the apo state or GHRH-bound state in complex with the Gs protein, molecular dynamics simulations reveal that the N termini of GHRHR and SV1 differentiate the downstream signaling pathways, Gs versus beta-arrestins. As suggested by mutagenesis and functional studies, it appears that GHRH-elicited signal bias toward beta-arrestin recruitment is constitutively mediated by SV1. The level of SV1 expression in prostate cancer cells is also positively correlated with ERK1/2 phosphorylation but negatively correlated with cAMP response. Our findings imply that constitutive signal bias may be a mechanism that ensures cancer cell proliferation.
WOS关键词HORMONE-RELEASING-HORMONE ; CANCER-CELLS ; INHIBIT GROWTH ; RECEPTOR ; ANTAGONISTS ; EXPRESSION ; ACTIVATION ; SPLICE-VARIANT-1 ; PROLIFERATION ; ENVIRONMENT
资助项目National Natural Science Foundation of China[81872915] ; National Natural Science Foundation of China[82073904] ; National Natural Science Foundation of China[81773792] ; National Natural Science Foundation of China[81973373] ; National Natural Science Foundation of China[21704064] ; National Science to Technology Major Project of China-Key New Drug Creation and Manufacturing Program[2018ZX09735-001] ; National Science to Technology Major Project of China-Key New Drug Creation and Manufacturing Program[2018ZX09711002-002-005] ; National Key Basic Research Program of China[2018YFA0507000] ; Shanghai Municipal Science and Technology Major Project[2019SHZDZX02] ; Ministry of Science and Technology of China Major Project[XDB08020303] ; Novo Nordisk-Chinese Academy of Sciences (CAS) Research Fund[NNCAS-2017-1-CC] ; Youth Innovation Promotion Association of CAS[2018319] ; CAS Enrollment ; Sanofi-Aventis-Shanghai Institutes for Biological Sciences Scholarship Program
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000705930300019
出版者NATL ACAD SCIENCES
源URL[http://119.78.100.183/handle/2S10ELR8/298448]  
专题新药研究国家重点实验室
通讯作者Xu, H. Eric; Cheng, Xi; Yang, Dehua; Wang, Ming-Wei
作者单位1.Fudan Univ, Sch Basic Med Sci, Dept Pharmacol, Shanghai 200032, Peoples R China
2.Fudan Univ, Sch Pharm, Shanghai 201203, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China
4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
6.Huazhong Univ Sci & Technol, Sch Artificial Intelligence & Automat, Wuhan 430074, Peoples R China
7.Zhejiang Univ, Dept Biophys, Sch Med, Hangzhou 310058, Peoples R China
8.Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
9.Fudan Univ, Eye & ENT Hosp, Shanghai 200031, Peoples R China
10.Chinese Acad Sci, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Cong, Zhaotong,Zhou, Fulai,Zhang, Chao,et al. Constitutive signal bias mediated by the human GHRHR splice variant 1[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,2021,118(40):10.
APA Cong, Zhaotong.,Zhou, Fulai.,Zhang, Chao.,Zou, Xinyu.,Zhang, Huibing.,...&Wang, Ming-Wei.(2021).Constitutive signal bias mediated by the human GHRHR splice variant 1.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,118(40),10.
MLA Cong, Zhaotong,et al."Constitutive signal bias mediated by the human GHRHR splice variant 1".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 118.40(2021):10.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。