Evidence map›Paper›PMID 33950683›Full record

ArticleJournal of proteome research2021

Mapping Angiotensin II Type 1 Receptor-Biased Signaling Using Proximity Labeling and Proteomics Identifies Diverse Actions of Biased Agonists.

Conrad T Pfeiffer, Jialu Wang, Joao A Paulo, Xue Jiang, Steven P Gygi, Howard A Rockman

Open access · greenAbstract read
In one paragraph

Article in Journal of proteome research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.4field-weighted citation impact, top 19% 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

14 citing papers in PubMed, 21 citations in OpenAlex.

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  11. G protein-coupled receptor signaling: transducers and effectors.American journal of physiology. Cell physiology · 2022
    Review
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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

6 authors at 3 institutions in 1 country.

Conrad T PfeifferDepartment of Medicine, Duke University Medical Center, Durham, North Carolina 27710, United States.
Jialu WangDepartment of Medicine, Duke University Medical Center, Durham, North Carolina 27710, United States.
Joao A PauloDepartment of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.
Xue JiangDepartment of Medicine, Duke University Medical Center, Durham, North Carolina 27710, United States.
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, United States.ORCID 0000-0001-7626-0034
Howard A RockmanDepartment of Medicine, Duke University Medical Center, Durham, North Carolina 27710, United States.ORCID 0000-0003-2921-1584
Duke Medical Center · USHarvard University · USDuke University · US

Funding

Regulation of Beta-Adrenergic Receptor Signaling by S-NitrosylationP01HL075443 · NHLBI · DUKE UNIVERSITY · PI STAMLER, JONATHAN S. · 2004 to 2019
$26.1M
MECHANISMS OF MALADAPTATION IN HEART FAILURER01HL056687 · NHLBI · UNIVERSITY OF NORTH CAROLINA CHAPEL HILL · PI Howard A Rockman · 1996 to 2026
$12.3M
New Sample Multiplexing Technologies to Identify Chemical Probes and Illuminate Ubiquitin BiologyR01GM067945 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GYGI, STEVEN P · 2003 to 2024
$10.5M
MULTIDISCIPLINARY HEART &VASCULAR DISEASEST32HL007101 · NHLBI · DUKE UNIVERSITY · PI FREEDMAN, NEIL J. · 1985 to 2020
$9.8M
Advancing Multiplexed Isobaric Tag-based Strategies for Proteome ProfilingR01GM132129 · NIGMS · HARVARD MEDICAL SCHOOL · PI PAULO, JOAO A · 2019 to 2023
$1.7M
NHLBI NIH HHS P01 HL075443NHLBI NIH HHS R01 HL056687NHLBI NIH HHS T32 HL007101NIGMS NIH HHS R01 GM067945NIGMS NIH HHS R01 GM132129
6 · The paper itself

Abstract

Angiotensin II type 1 receptors (AT1Rs) are one of the most widely studied G-protein-coupled receptors. To fully appreciate the diversity in cellular signaling profiles activated by AT1R transducer-biased ligands, we utilized peroxidase-catalyzed proximity labeling to capture proteins in close proximity to AT1Rs in response to six different ligands: angiotensin II (full agonist), S1I8 (partial agonist), TRV055 and TRV056 (G-protein-biased agonists), and TRV026 and TRV027 (β-arrestin-biased agonists) at 90 s, 10 min, and 60 min after stimulation (ProteomeXchange Identifier PXD023814). We systematically analyzed the kinetics of AT1R trafficking and determined that distinct ligands lead AT1R to different cellular compartments for downstream signaling activation and receptor degradation/recycling. Distinct proximity labeling of proteins from a number of functional classes, including GTPases, adaptor proteins, and kinases, was activated by different ligands suggesting unique signaling and physiological roles of the AT1R. Ligands within the same class, that is, either G-protein-biased or β-arrestin-biased, shared high similarity in their labeling profiles. A comparison between ligand classes revealed distinct signaling activation such as greater labeling by G-protein-biased ligands on ESCRT-0 complex proteins that act as the sorting machinery for ubiquitinated proteins. Our study provides a comprehensive analysis of AT1R receptor-trafficking kinetics and signaling activation profiles induced by distinct classes of ligands.

Indexed as

ProteomicsReceptor, Angiotensin, Type 1beta-ArrestinsLigandsSignal Transductionbeta-ArrestinsLigandsReceptor, Angiotensin, Type 1APEXAT1Rbiased agonismproximity labeling

Identifiers

PMID33950683
PMCPMC8218870
OpenAlexW3158761314

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.