PXD012908 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
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 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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD012908
- Label: PRIDE project
- Name: Agonist-selective NOP receptor phosphorylation correlates in vitro and in vivo and reveals differential post-activation signaling by chemically diverse agonists