PXD012908

PXD012908 is an original dataset announced via ProteomeXchange.

Title	Agonist-selective NOP receptor phosphorylation correlates in vitro and in vivo and reveals differential post-activation signaling by chemically diverse agonists
Description	Agonists for the nociceptin/orphanin FQ opioid peptide NOP receptor, a member of the opioid receptor family, are under active investigation as novel analgesics, but their modes of signaling are less well characterized than those for other members of the opioid receptor family. Therefore, we investigated whether different NOP receptor ligands show differential signaling or functional selectivity at the NOP receptor. Using newly developed phosphosite-specific antibodies to NOP receptor, we found that agonist-induced NOP receptor phosphorylation occurred primarily at four carboxyl-terminal serine (S) and threonine (T) residues, namely Ser346, Ser351, Thr362 and Ser363, and proceeded with a temporal hierarchy, with Ser346 as the first site of phosphorylation. G protein-coupled receptor kinases 2 and 3 (GRK2/3) cooperated during agonist-induced phosphorylation, which in turn facilitated NOP receptor desensitization and internalization. A comparison of structurally distinct NOP receptor agonists revealed dissociation in functional efficacies between G protein-dependent signaling and receptor phosphorylation. Furthermore, in vivo, in NOP-eGFP and NOP-eYFP mice, NOP receptor agonists induced multisite phosphorylation and internalization in a dose-dependent and agonist-selective manner that could be blocked by specific antagonists. Together, our study provides novel tools to study ligand-activated NOP receptor signaling in vitro and in vivo. Differential agonist-selective NOP receptor phosphorylation by chemically diverse NOP receptor agonists suggests that differential signaling by NOP receptor agonists may play a role in NOP receptor ligand pharmacology.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:05:06.291.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Carine Froment
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-28 06:25:43	ID requested
1	2020-05-26 13:26:39	announced
⏵ 2	2024-10-22 05:05:14	announced	2024-10-22: Updated project metadata.

Mann A, Moul, é, dous L, Froment C, O'Neill PR, Dasgupta P, G, ü, nther T, Brunori G, Kieffer BL, Toll L, Bruchas MR, Zaveri NT, Schulz S, Agonist-selective NOP receptor phosphorylation correlates in vitro and in vivo and reveals differential post-activation signaling by chemically diverse agonists. Sci Signal, 12(574):(2019) [pubmed]

10.1126/scisignal.aau8072;

submitter keyword: Brain, Opioid receptor family, Mouse,Biological, Pharmacology, Post-Translational Modification, NanoLC-MS/MS CID/ETD, Phosphorylation

Stefan Schulz
contact affiliation	Institute of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, Drackendorfer Str. 1, 07747, Jena, Germany
contact email	Stefan.Schulz@med.uni-jena.de
lab head
Carine Froment
contact affiliation	IPBS-CNRS
contact email	carine.froment@ipbs.fr
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/2020/05/PXD012908

PRIDE project URI

• PRIDE
  1. PXD012908
     1. Label: PRIDE project
     2. Name: Agonist-selective NOP receptor phosphorylation correlates in vitro and in vivo and reveals differential post-activation signaling by chemically diverse agonists