PXD025327

PXD025327 is an original dataset announced via ProteomeXchange.

Title	In vitro reconstitution of Sgk3 activation by phosphatidylinositol-3-phosphate
Description	Serum- and glucocorticoid-regulated kinase 3 (Sgk3) is activated by the phospholipid 19 phosphatidylinositol-3-phosphate (PI3P) downstream of growth factor signaling and 20 by Vps34-mediated PI3P production during autophagy. Upregulation of Sgk3 activity 21 has been linked to a number of human cancers due to its overlapping substrate 22 specificity with Akt. Here, we show that Sgk3 is regulated by a combination of 23 phosphorylation and allosteric activation by PI3P. We demonstrate that Sgk3 is 24 specifically activated by PI3P and that PI3P binding induces large conformational 25 changes in Sgk3. Using Vps34 and liposomes containing phosphatidylinositol, we 26 reconstitute Sgk3 signaling via Vps34-mediated PI3P synthesis in vitro. In addition to 27 defining the mechanism of Sgk3 activation by PI3P, our findings open up potential 28 therapeutic avenues in allosteric inhibitor development to target Sgk3 in cancer.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:29:31.806.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	John Burke
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	impact HD

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-12 19:16:10	ID requested
1	2021-09-22 10:11:45	announced
⏵ 2	2024-10-22 05:29:32	announced	2024-10-22: Updated project metadata.

Pokorny D, Truebestein L, Fleming KD, Burke JE, Leonard TA, vitro reconstitution of Sgk3 activation by phosphatidylinositol 3-phosphate. J Biol Chem, 297(2):100919(2021) [pubmed]

10.1016/j.jbc.2021.100919;

submitter keyword: kinase,Sgk3, HDX-MS, PI3P

Dr. John E Burke
contact affiliation	University of Victoria
contact email	jeburke@uvic.ca
lab head
John Burke
contact affiliation	University of Victoria
contact email	jeburke@uvic.ca
dataset submitter

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://ftp.pride.ebi.ac.uk/pride/data/archive/2021/09/PXD025327

PRIDE project URI

• PRIDE
  1. PXD025327
     1. Label: PRIDE project
     2. Name: In vitro reconstitution of Sgk3 activation by phosphatidylinositol-3-phosphate