PXD005803-1

PXD005803 is an original dataset announced via ProteomeXchange.

Title	Large-scale phosphoproteomics reveals Shp-2 phosphatase-dependent regulators of Pdgf-receptor signaling
Description	Despite its low cellular abundance, tyrosine phosphorylation (pTyr) regulates numerous cell signaling pathways in health and disease. We applied comprehensive phosphoproteomics to unravel differential regulators of receptor tyrosine kinase (RTK)–initiated signaling networks upon activation by Pdgf-ββ, Fgf-2, or Igf-1, and identified over 40,000 phosphorylation sites, including many phosphotyrosine sites without additional enrichment. The analysis revealed RTK-specific regulation of hundreds of pTyr sites on key signaling molecules. We found the tyrosine phosphatase Shp2 to be the master regulator of Pdgfr pTyr signaling. Application of a recently introduced allosteric Shp2 inhibitor revealed global regulation of the Pdgf-dependent tyrosine phosphoproteome, which significantly impaired cell migration. Additionally, we present a list of hundreds of Shp2-dependent targets and putative substrates including Rasa1 and Cortactin with increased tyrosine phosphorylation, and Gab1 and Erk1/2 with decreased tyrosine phosphorylation. Our study demonstrates that large-scale quantitative phosphoproteomics can precisely dissect tightly regulated kinase-phosphatase signaling networks.
HostingRepository	PRIDE
AnnounceDate	2018-03-08
AnnouncementXML	Submission_2018-03-07_23:52:52.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tanveer Batth
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	amidated residue; phosphorylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-01-30 02:41:34	ID requested
⏵ 1	2018-03-07 23:52:53	announced
2	2018-03-08 07:05:14	announced	Updated project metadata.
3	2018-03-12 02:31:37	announced	Updated project metadata.
4	2024-10-22 04:36:03	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: Phosphoproteomics, Shp-2, PDGF, SHP099, Q-Exactive, Orbitrap, Label-Free Quantitation, Tyrosine phosphorylation, TiO2, Mass Spectrometry

Jesper Velgaard Olsen
contact affiliation	Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Science, University of Copenhagen
contact email	jesper.olsen@cpr.ku.dk
lab head
Tanveer Batth
contact affiliation	Novo Nordisk Center for Protein Research, University of Copenhagen
contact email	t.batth@cpr.ku.dk
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/2018/03/PXD005803

PRIDE project URI

• PRIDE
  1. PXD005803
     1. Label: PRIDE project
     2. Name: Large-scale phosphoproteomics reveals Shp-2 phosphatase-dependent regulators of Pdgf-receptor signaling