Evidence map›Paper›PMID 38481681›Full record

ArticleACS pharmacology & translational science2024

Evolutionary Identification of the Requirement of the Second Intracellular Loop for the Constitutive Activity of Melanocortin-4 Receptors.

Bingxin Xu, Jindong Yao, Wenqi Song, Xinyi Yan, Ming Zhu, Jiangtao Li, Zhonglin Ma, Yanchuan Li, Yihao Li, Yanbin Fu and 4 more

Open access · greenAbstract read
In one paragraph

Article in ACS pharmacology & translational science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.5field-weighted citation impact, top 40% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 3 institutions in 1 country.

Bingxin XuFundamental Research Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Life Sciences and Technology, Tongji University, Shanghai 201619, P.R. China.
Jindong YaoFundamental Research Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Life Sciences and Technology, Tongji University, Shanghai 201619, P.R. China.
Wenqi SongFundamental Research Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Life Sciences and Technology, Tongji University, Shanghai 201619, P.R. China.
Xinyi YanFundamental Research Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Life Sciences and Technology, Tongji University, Shanghai 201619, P.R. China.
Ming ZhuFundamental Research Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Life Sciences and Technology, Tongji University, Shanghai 201619, P.R. China.
Jiangtao LiState Key Laboratory of Marine Geology, School of Ocean and Earth Science, Tongji University, Shanghai 200092, P.R. China.
Zhonglin MaState Key Laboratory of Marine Geology, School of Ocean and Earth Science, Tongji University, Shanghai 200092, P.R. China.
Yanchuan LiHubei Topgene Research Institute of Hubei Topgene Biotechnology Co., Ltd., East Lake High-Tech Development Zone, Wuhan 430205, P.R. China.
Yihao LiHubei Topgene Research Institute of Hubei Topgene Biotechnology Co., Ltd., East Lake High-Tech Development Zone, Wuhan 430205, P.R. China.
Yanbin FuShanghai Cancer Institute, Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China.
Liu LiuShanghai Yuhui Pharmaceutical Technology (Group) Co., Ltd., and Shanghai Ruishen Technology Development Co., Ltd., Shanghai 201203, P.R. China.
Lei LiDepartment of Orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, P.R. China.
Jianjun LyuHubei Topgene Research Institute of Hubei Topgene Biotechnology Co., Ltd., East Lake High-Tech Development Zone, Wuhan 430205, P.R. China.
Chao ZhangFundamental Research Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Life Sciences and Technology, Tongji University, Shanghai 201619, P.R. China.ORCID https://orcid.org/0000-0001-6418-8370
Shanghai Sunshine Rehabilitation Center · CNShanghai Jiao Tong University · CNTongji University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Melanocortin-4 receptor (MC4R) functions as a crucial neuroendocrine G protein-coupled receptor (GPCR) in the central nervous system of mammals, displaying agonist-independent constitutive activity that is mainly determined by its N-terminal domain. We previously reported that zebrafish MC4R exhibited a much higher basal cAMP level in comparison to mammalian MC4Rs. However, the functional evolution of constitutive activities in chordate MC4Rs remains to be elucidated. Here we cloned and compared the constitutive activities of MC4Rs from nine vertebrate species and showed that the additive action of the N-terminus with the extracellular region or transmembrane domain exhibited a combined pharmacological effect on the MC4R constitutive activity. In addition, we demonstrated that four residues of F149, Q156, V163, and K164 of the second intracellular loop played a vital role in determining MC4R constitutive activity. This study provided novel insights into functional evolution and identified a key motif essential for constitutive modulation of MC4R signaling.

Identifiers

PMID38481681
PMCPMC10928900
OpenAlexW4391844620

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.