PXD034033-1

PXD034033 is an original dataset announced via ProteomeXchange.

Title	Phosphorylation barcodes encoded by CXCR3 agonists direct biased chemokine signaling
Description	Chemokine receptors (CKRs), a class of G protein-coupled receptors (GPCRs), interact with transducers like G proteins and β-arrestins. Many chemokines act as “biased agonists” that activate certain transducers over others. There has been limited success in pharmacologically targeting CKRs, with little evidence that differential receptor phosphorylation, or “phosphorylation barcodes,” direct biased responses. Here, we used mass spectrometry to demonstrate that CXCR3 chemokines generate different phosphorylation barcodes associated with differential activation of transducers. Chemokine stimulation resulted in distinct changes throughout the kinome in global phosphoproteomic studies. Mutation of CXCR3 phosphosites altered β-arrestin conformation and activation in molecular dynamics simulations. T-cells expressing phosphorylation-deficient CXCR3 mutants resulted in agonist- and receptor-specific chemotactic profiles not completely explained by engagement of G proteins and β-arrestins. Our results demonstrate that CXCR3 chemokines act as biased agonists through differential encoding of phosphorylation barcodes, and highlight the limitations of assessing GPCR physiology with proximal effector activity alone.
HostingRepository	jPOST
AnnounceDate	2023-05-24
AnnouncementXML	Submission_2023-05-23_08:00:04.528.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Chia-Feng Tsai
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	S-carboxamidomethyl-L-cysteine; L-methionine sulfoxide; unknown modification; unknown modification; alpha-amino acetylated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2022-05-23 16:35:17	ID requested
⏵ 1	2023-05-23 08:00:04	announced

Dataset with its publication pending

submitter keyword: CXCR3, Barcodes, Phosphoproteome, IMAC,

Sudarshan Rajagopal
lab head
Chia-Feng Tsai
contact affiliation	Pacific Northwest National Laboratory
dataset submitter

jPOST dataset URI

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