PXD010687

PXD010687 is an original dataset announced via ProteomeXchange.

Title	Characterization of the Src-regulated kinome identifies SGK1 as a key mediator of Src-induced transformation
Description	Despite significant progress, our understanding of how specific oncogenes transform cells is still limited and likely underestimates the complexity of downstream signalling events. Herein, we describe a novel, integrated approach that addresses this knowledge gap. This utilizes mass spectrometry-based chemical proteomics to characterize the global impact of an oncogene on the expressed kinome, and then functionally annotates the regulated kinases. As an example, we identified approximately seventy protein kinases exhibiting altered expression and/or phosphorylation in Src-transformed mammary epithelial cells. An integrated siRNA screen identified nine kinases, including SGK1, as being essential for Src-induced transformation. In triple negative breast cancer cells, which exhibit a prominent signalling network governed by src family kinases, Src positively regulated SGK1 expression and combined inhibition of Src and SGK1 was more effective at inhibiting colony formation in vitro, and xenograft growth in vivo, than either treatment alone. Therefore, this approach not only provides major mechanistic insights into oncogenic transformation but also aids the design of improved therapeutic strategies.
HostingRepository	PRIDE
AnnounceDate	2019-01-14
AnnouncementXML	Submission_2019-01-25_05:08:46.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Hugh Ma
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive; LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2018-08-06 03:09:42	ID requested
1	2019-01-14 01:41:00	announced
⏵ 2	2019-01-25 05:08:48	announced	Updated publication reference for PubMed record(s): 30655532.

Ma X, Zhang L, Song J, Nguyen E, Lee RS, Rodgers SJ, Li F, Huang C, Schittenhelm RB, Chan H, Chheang C, Wu J, Brown KK, Mitchell CA, Simpson KJ, Daly RJ, Characterization of the Src-regulated kinome identifies SGK1 as a key mediator of Src-induced transformation. Nat Commun, 10(1):296(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: kinome, cancer, breast cancer, src

Roger Daly
contact affiliation	Monash University
contact email	roger.daly@monash.edu
lab head
Hugh Ma
contact affiliation	Monash University
contact email	hugh.ma@monash.edu
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/2019/01/PXD010687

PRIDE project URI

• PRIDE
  1. PXD010687
     1. Label: PRIDE project
     2. Name: Characterization of the Src-regulated kinome identifies SGK1 as a key mediator of Src-induced transformation