PXD006637-2

PXD006637 is an original dataset announced via ProteomeXchange.

Title	In vivo Brain GPCR Signaling Elucidated by Phosphoproteomics
Description	Obtaining a systems view of G protein-coupled receptor (GPCR) signaling in its native environment is the key in development of GPCR therapeutics with fewer side effects. Using the kappa opioid receptor (KOR) as model GPCR, we employed high-throughput phosphoproteomics to investigate downstream signaling induced by structurally diverse agonists in five mouse brain-regions. Through quantification of 50,000 different phosphosites, this approach yielded a systems view of KOR in vivo signaling, revealing novel mechanisms of drug action. Pathway-selective agonists elicited differential dynamic phosphorylation of synaptic proteins, linking GPCR signaling to modulation of brain functions. We also discovered enrichment of mTOR pathway in agonists associated with aversion, a side effect. Consequently, mTOR inhibition during KOR activation abolished aversion, while preserving therapeutic analgesic and anticonvulsant effects. Our results establish high-throughput phosphoproteomics as a general strategy to investigate GPCR in vivo signaling, enabling prediction and modulation of behavioral outcomes.
HostingRepository	PRIDE
AnnounceDate	2018-06-15
AnnouncementXML	Submission_2018-06-24_23:52:47.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jeffrey Liu
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-06-01 00:17:21	ID requested
1	2018-06-15 02:29:24	announced
⏵ 2	2018-06-24 23:52:49	announced	Updated publication reference for PubMed record(s): 29930108.
3	2024-10-22 04:43:52	announced	2024-10-22: Updated project metadata.

Liu JJ, Sharma K, Zangrandi L, Chen C, Humphrey SJ, Chiu YT, Spetea M, Liu-Chen LY, Schwarzer C, Mann M, In vivo brain GPCR signaling elucidated by phosphoproteomics. Science, 360(6395):(2018) [pubmed]

curator keyword: Biological

submitter keyword: GPCR brain phosphoproteomics

Matthias Mann
contact affiliation	Max-Planck-Institute of Biochemistry
contact email	mmann@biochem.mpg.de
lab head
Jeffrey Liu
contact affiliation	Max Planck Institute of Biochemistry
contact email	jliu@biochem.mpg.de
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/2018/06/PXD006637

PRIDE project URI

• PRIDE
  1. PXD006637
     1. Label: PRIDE project
     2. Name: In vivo Brain GPCR Signaling Elucidated by Phosphoproteomics