PXD028167-1
PXD028167 is an original dataset announced via ProteomeXchange.
Dataset Summary
Title | S6K1-mediated phosphorylation of PDK1 impairs AKT kinase activity and oncogenic functions |
Description | Functioning as a master kinase, 3-phosphoinositide-dependent protein kinase 1 (PDK1) plays a fundamental role in phosphorylating and activating protein kinases A, B and C (AGC) family kinases, including AKT. However, upstream regulation of PDK1 remains largely elusive. Here we report that ribosomal protein S6 kinase beta 1 (S6K1), a member of AGC kinases and downstream target of mechanistic target of rapamycin complex 1 (mTORC1), directly phosphorylates PDK1 at its pleckstrin homology (PH) domain, and impairs PDK1 interaction with and activation of AKT. Mechanistically, S6K1-mediated phosphorylation of PDK1 augments its interaction with 14-3-3 adaptor protein and homo-dimerization, subsequently dissociating PDK1 from phosphatidylinositol 3,4,5 triphosphate (PIP3) and retarding its interaction with AKT. Pathologically, tumor patient-associated PDK1 mutations, either attenuating S6K1-mediated PDK1 phosphorylation or impairing PDK1 interaction with 14-3-3, result in elevated AKT kinase activity and oncogenic functions. Taken together, our findings not only unravel a delicate feedback regulation of AKT signaling via S6K1-mediated PDK1 phosphorylation, but also highlight the potential strategy to combat mutant PDK1-driven cancers. |
HostingRepository | iProX |
AnnounceDate | 2021-08-27 |
AnnouncementXML | Submission_2021-08-27_00:38:48.916.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Jianping Guo |
SpeciesList | scientific name: Homo sapiens; NCBI TaxID: 9606; |
ModificationList | phosphorylated residue |
Instrument | Q Exactive HF |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
---|---|---|---|
0 | 2021-08-27 00:38:36 | ID requested | |
⏵ 1 | 2021-08-27 00:38:49 | announced | |
2 | 2022-10-21 02:41:33 | announced | 2022-10-21: Update publication information. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: PDK1, S6K |
Contact List
Jianping Guo | |
---|---|
contact affiliation | Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University |
contact email | guojp6@mail.sysu.edu.cn |
lab head | |
Jianping Guo | |
contact affiliation | Institute of Precision Medicine, the First Affiliated Hospital, Sun Yat-sen University |
contact email | guojp6@mail.sysu.edu.cn |
dataset submitter |
Full Dataset Link List
iProX dataset URI |