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

{"sci_version": "1.0", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33950683", "kind": "science-record", "revision": 3, "content_hash": "sha256:f39204f055774aa41f092b96471fdcbe6480bb928eb125de84381de23a11dd05", "created_at": "2026-11-01T17:35:14Z", "updated_at": "2026-11-01T21:25:17Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Mapping Angiotensin II Type 1 Receptor-Biased Signaling Using Proximity Labeling and Proteomics Identifies Diverse Actions of Biased Agonists.", "doi": "10.1021/acs.jproteome.1c00080", "pmid": "33950683", "authors": ["Conrad T Pfeiffer", "Jialu Wang", "Joao A Paulo", "Xue Jiang", "Steven P Gygi", "Howard A Rockman"], "journal": "Journal of proteome research", "year": 2021, "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.", "claims": [{"id": "claim-method", "statement": "Volcano plots were made by first making 1v1 comparisons between ligands in log 2 space and p-values were calculated with an independent two-tailed T-test.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33950683", "locator": "sections[10] \"Post-mass Spectrometry Data Analysis\" paragraph 2", "quote": "Volcano plots were made by first making 1v1 comparisons between ligands in log 2 space and p-values were calculated with an independent two-tailed T-test."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE24 partner repository with the dataset identifier PXD023814.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33950683", "locator": "sections[8] \"Liquid Chromatography and Tandem Mass Spectrometry\" paragraph 2", "quote": "The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE24 partner repository with the dataset identifier PXD023814."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33950683"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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