PXD002065

PXD002065 is an original dataset announced via ProteomeXchange.

Title	TK SILACepedia
Description	Tyrosine kinases (TKs) are central regulators in cellular activities and perturbations of TK signaling contribute to oncogenesis. However, less than half of the TKs have been thoroughly studied and a global functional analysis of their proteomic portrait is lacking. Here we conducted a combined approach of RNAi and stable isotope labeling with amino acids in cell culture (SILAC)-based quantitative proteomics to decode the TK-regulated proteome and associated signaling dynamics. As a result, a broad proteomic repertoire modulated by TKs was revealed, upon silencing of the 65 TKs expressed in MCF-7 breast cancer cells. This yielded 10 new distinctive TK clusters according to similarity in TK-regulated proteome, each characterized by a unique signaling signature in contrast to previous classifications. We provide functional analyses and identify critical pathways for each cluster based on their common downstream targets. Analysis of different breast cancer subtypes demonstrated distinct correlations of each cluster with clinical outcome. From the significantly up- and down-regulated proteins, we identified a number of markers of drug sensitivity and resistance. These data supports the role of TKs in regulating major aspects of cellular activity, but also reveals redundancy in signaling, explaining why kinase inhibitors alone often fail to achieve their clinical aims. The TK-SILACepedia provides a comprehensive resource for studying the global function of TKs in cancer.
HostingRepository	PRIDE
AnnounceDate	2015-06-23
AnnouncementXML	Submission_2015-06-23_09:20:47.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Georgios Giamas
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2015-04-14 02:18:59	ID requested
⏵ 1	2015-06-23 09:20:48	announced

Stebbing J, Zhang H, Xu Y, Grothey A, Ajuh P, Angelopoulos N, Giamas G, Characterization of the Tyrosine Kinase-Regulated Proteome in Breast Cancer by Combined use of RNA interference (RNAi) and Stable Isotope Labeling with Amino Acids in Cell Culture (SILAC) Quantitative Proteomics. Mol Cell Proteomics, 14(9):2479-92(2015) [pubmed]

curator keyword: Biomedical

submitter keyword: SILAC tyrosine kinases breast cancer cell signaling

Georgios Giamas
contact affiliation	Imperial College, London
contact email	g.giamas@imperial.ac.uk
lab head
Georgios Giamas
contact affiliation	Imperial College
contact email	g.giamas@imperial.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD002065
     1. Label: PRIDE project
     2. Name: TK SILACepedia