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PXD025031-1

PXD025031 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleSelective inhibition reveals the regulatory function of DYRK2 in protein synthesis and calcium entry
DescriptionThe dual-specificity tyrosine phosphorylation-regulated kinase DYRK2 has emerged as a key regulator of cellular processes such as proteasome-mediated protein degradation. To gain further insights into its function, we took a chemical biology approach and developed C17, a potent small-molecule DYRK2 inhibitor, through multiple rounds of structure-based optimization guided by a number of co-crystallized structures. C17 displayed an effect on DYRK2 at a single-digit nanomolar IC50 and showed outstanding selectivity for the human kinome containing 467 other human kinases. Using C17 as a chemical probe, we further performed quantitative phosphoproteomic assays and identified several novel DYRK2 targets, including eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) and stromal interaction molecule 1 (STIM1). DYRK2 phosphorylated 4E-BP1 at multiple sites, and the combined treatment of C17 with AKT and MEK inhibitors showed synergistic 4E-BP1 phosphorylation suppression. The phosphorylation of STIM1 by DYRK2 substantially increased the interaction of STIM1 with the ORAI1 channel, and C17 impeded the store-operated calcium entry process. Collectively, these studies further expand our understanding of DYRK2 and provide a valuable tool to further pinpoint its biological function.
HostingRepositoryMassIVE
AnnounceDate2021-03-26
AnnouncementXMLSubmission_2021-03-26_09:46:16.860.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterMaoYiheng
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListPhospho
InstrumentQ Exactive HF-X
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-03-26 09:41:51ID requested
12021-03-26 09:46:17announced
Publication List
no publication
Keyword List
submitter keyword: DYRK2
Contact List
Xiaoguang Lei
contact affiliationpeking university
contact emailxglei@pku.edu.cn
lab head
MaoYiheng
contact affiliationSUSTech
contact email11849427@mail.sustech.edu.cn
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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