PXD014561

PXD014561 is an original dataset announced via ProteomeXchange.

Title	Identification of Syntaxin 7 and 12 as the first selective substrates for SGK3
Description	Deregulation of the PI3K/Akt pathway is a common feature in many types of cancer. Recent data has demonstrated that prolonged inhibition of breast cancer cell lines with PI3K and Akt inhibitors leads to up-regulation and increased activity of the AGC kinase Serum and glucocorticoid activated kinase 3, SGK3, which in turn substitutes for Akt and leads to activation of mTORC1. SGK3 and Akt exhibit similar substrate specificity for Ser/Thr residues in the RxRxxS/T motif. However, SGK3 can be regulated by both PI3K class I and class III and possesses a unique PX domain, enabling it to bind to PI(3)P lipids in endosomes. Still, the known SGK3 substrates are either shared or have not been tested whether Akt can phosphorylate them. In the present study, we undertook genetic and pharmacologic phosphoproteomic screens to search for selective SGK3 substrates. We identified a significant number of potential in vivo SGK3 selective substrates, including the endosomal proteins STX7, STX12, RFIP4 and WDR44. In vitro phosphorylation studies demonstrated that these substrates were directly phosphorylated at the sites identified in vivo by SGK3 but, unlike all other SGK3 substrates reported, not by Akt. We provide evidence that endogenous STX7 and STX12 are physiological SGK3 substrates whose phosphorylation is potently stimulated by IGF1. Our data pinpoint that STX7 and STX12 are the first selective SGK3 substrates in vivo and this phosphorylation enhances their interaction with the respective SNARE complexes. Finally, we suggest that STX7 and STX12 phosphorylation can be utilised as in vivo biomarkers for SGK3 activity.
HostingRepository	PRIDE
AnnounceDate	2020-05-26
AnnouncementXML	Submission_2020-05-26_15:20:13.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Raja Sekhar Nirujogi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2019-07-10 09:00:06	ID requested
⏵ 1	2020-05-26 15:20:14	announced

Malik N, Nirujogi RS, Peltier J, Macartney T, Wightman M, Prescott AR, Gourlay R, Trost M, Alessi DR, Karapetsas A, Phosphoproteomics reveals that the hVPS34 regulated SGK3 kinase specifically phosphorylates endosomal proteins including Syntaxin-7, Syntaxin-12, RFIP4 and WDR44. Biochem J, 476(20):3081-3107(2019) [pubmed]

submitter keyword: SGK3, Phosphoprpteomis, STX7 and STX12

Prof Matthias Trost
contact affiliation	Faculty of Medical Sciences, Institute for Cell and Molecular Biosciences, Newcastle upon Tyne, UK
contact email	matthias.trost@newcastle.ac.uk
lab head
Raja Sekhar Nirujogi
contact affiliation	MRC Protein Phosphorylation Unit, university of Dundee
contact email	rnirujogi@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD014561
     1. Label: PRIDE project
     2. Name: Identification of Syntaxin 7 and 12 as the first selective substrates for SGK3