PXD037472

PXD037472 is an original dataset announced via ProteomeXchange.

Title	GPCR signaling neighborhoods associate with the susceptibility to adverse drug reactions of incretin mimetics
Description	G protein-coupled receptors are important drug targets that engage and activate signaling transducers in multiple cellular compartments. Delineating therapeutic signaling from signaling associated with adverse events is an important step towards rational drug design. The glucagon-like peptide-1 receptor (GLP-1R) is a validated target for the treatment of diabetes and obesity, but drugs that target this receptor are a frequent cause of adverse events. Using recently developed biosensors, we explored the ability of GLP-1R to activate 15 pathways in 4 cellular compartments and demonstrate that modifications aimed at improving the therapeutic potential of GLP-1R agonists greatly influence compound efficacy, potency and safety in a pathway- and compartment-selective manner. These findings, together with comparative structure analysis, time-lapse microscopy and phosphoproteomics, reveal unique signaling signatures for GLP-1R agonists at the level of receptor conformation, functional selectivity and location bias, thus associating signaling neighborhoods with functionally distinct cellular outcomes and clinical consequences.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:33:43.843.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Pierre Sabatier
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-10-17 01:11:07	ID requested
1	2023-10-11 05:44:55	announced
⏵ 2	2023-11-14 08:33:44	announced	2023-11-14: Updated project metadata.

Dataset with its publication pending

submitter keyword: compartmentalized signaling, GLP-1R, functional selectivity, incretin mimetics, adverse drug reactions,GPCR, BRET

Volker M. Lauschke
contact affiliation	Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm, Sweden Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany University of Tübingen, Tübingen, Germany
contact email	volker.lauschke@ki.se
lab head
Pierre Sabatier
contact affiliation	Department of Surgical Sciences, Uppsala University. Novo Nordisk Foundation Center for Protein Research, University of Copenhagen.
contact email	pierre63.sabatier@gmail.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/10/PXD037472

PRIDE project URI

• PRIDE
  1. PXD037472
     1. Label: PRIDE project
     2. Name: GPCR signaling neighborhoods associate with the susceptibility to adverse drug reactions of incretin mimetics