<<< Full experiment listing

PXD023743

PXD023743 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_08:51:43.140.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
02021-01-21 18:07:34ID requested
12021-03-26 08:51:43announced
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
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://massive.ucsd.edu/MSV000086745/