PXD025031-1
PXD025031 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Selective inhibition reveals the regulatory function of DYRK2 in protein synthesis and calcium entry |
| Description | The 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. |
| HostingRepository | MassIVE |
| AnnounceDate | 2021-03-26 |
| AnnouncementXML | Submission_2021-03-26_09:46:16.860.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | MaoYiheng |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Phospho |
| Instrument | Q Exactive HF-X |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2021-03-26 09:41:51 | ID requested | |
| ⏵ 1 | 2021-03-26 09:46:17 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: DYRK2 |
Contact List
| Xiaoguang Lei | |
|---|---|
| contact affiliation | peking university |
| contact email | xglei@pku.edu.cn |
| lab head | |
| MaoYiheng | |
| contact affiliation | SUSTech |
| contact email | 11849427@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/MSV000087106/ |
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