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PXD012908

PXD012908 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleAgonist-selective NOP receptor phosphorylation correlates in vitro and in vivo and reveals differential post-activation signaling by chemically diverse agonists
DescriptionAgonists 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_05:05:06.291.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterCarine Froment
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap
Dataset History
RevisionDatetimeStatusChangeLog Entry
02019-02-28 06:25:43ID requested
12020-05-26 13:26:39announced
22024-10-22 05:05:14announced2024-10-22: Updated project metadata.
Publication List
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;
Keyword List
submitter keyword: Brain, Opioid receptor family, Mouse,Biological, Pharmacology, Post-Translational Modification, NanoLC-MS/MS CID/ETD, Phosphorylation
Contact List
Stefan Schulz
contact affiliationInstitute of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, Drackendorfer Str. 1, 07747, Jena, Germany
contact emailStefan.Schulz@med.uni-jena.de
lab head
Carine Froment
contact affiliationIPBS-CNRS
contact emailcarine.froment@ipbs.fr
dataset submitter
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Dataset FTP location
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