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PXD067830

PXD067830 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleGPCR kinases shape ACKR4 functions via differential C-terminal phosphorylation
DescriptionAtypical chemokine receptor 4 (ACKR40+) is a scavenger receptor that regulates the availability of chemokines, including CCL19, and consequently the responsiveness of their classical G protein coupled receptors. In contrast to classical chemokine receptors, ACKR4 is completely biased towards beta-arrestins and does not couple to G proteins. Here, we show that ACKR4 in its apo state constitutively pre-associates with beta-arrestins and cycles between the plasma membrane and endosomal compartments. We identify distinct serine and threonine residues in the tail region of ACKR4 involved in regulating steady-state receptor trafficking and chemokine uptake, and that a C-terminal serine/threonine cluster is key for both ligand-mediated beta-arrestin recruitment and efficient chemokine uptake. Moreover, different serine/threonine clusters in the tail region of ACKR4 account for steady-state and chemokine-driven association of the four non-visual GPCR kinases (GRKs), which differentially phosphorylate two serine and one threonine residues. We show that GRK5/6 primarily phosphorylate ACKR4 in the absence of chemokines, and that CCL19 stimulation recruits GRK2/3 to enhance ACKR4 phosphorylation. Notably, we found that GRK2 and GRK3 can interact with the heterotrimeric G protein without the need of its activation. Finally, we show that the C-terminal serine/threonine cluster of ACKR4 and GRK2 play leading roles in beta-arrestin recruitment and CCL19 internalisation.
HostingRepositoryMassIVE
AnnounceDate2026-04-13
AnnouncementXMLSubmission_2026-04-13_07:11:47.111.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRoland Bruderer
SpeciesList scientific name: human;
ModificationListPhospho
InstrumenttimsTOF HT
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-08-28 05:10:33ID requested
12026-04-13 07:11:47announced
Publication List
no publication
Keyword List
submitter keyword: gpcr, DatasetType:Proteomics
Contact List
David Legler
contact affiliationInstitute of Cell Biology and Immunology Thurgau
contact emaildaniel.legler@bitg.ch
lab head
Roland Bruderer
contact affiliationBiognosys AG
contact emailroland.bruderer@biognosys.com
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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