PXD011940 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Vascular endothelial protein tyrosine phosphatase: Identification of novel cell junction-related substrates and a ternary receptor complex with EPHB4 and TIE2 |
Description | Vascular endothelial protein tyrosine phosphatase (VE-PTP, PTPRB) is a receptor type phosphatase that is crucial for the regulation of endothelial junctions and blood vessel development. VE-PTP regulates vascular integrity by dephosphorylating substrates which are key players in endothelial junction stability, such as the angiopoietin receptor TIE2, the endothelial adherens junction protein VE-cadherin and the vascular endothelial growth factor receptor VEGFR2. Here, we have systematically searched for novel substrates of VE-PTP in endothelial cells by utilizing two approaches. First, we studied changes in the endothelial phosphoproteome upon exposing cells to a highly VE-PTP-specific phosphatase inhibitor followed by affinity isolation and mass-spectrometric analysis of phosphorylated proteins by phosphotyrosine-specific antibodies. Second, we used a substrate trapping mutant of VE-PTP to pull down phosphorylated substrates in combination with SILAC-based quantitative mass spectrometry measurements. We identified a set of substrate candidates of VE-PTP, of which a remarkably large fraction is related to cell junctions (48/165; 29.1%). Several of those were found in both screens and displayed very high connectivity in predicted functional interaction networks. The receptor protein tyrosine kinase EPHB4 was the most prominently phosphorylated protein upon VE-PTP inhibition among those VE-PTP targets that were identified by both proteomic approaches. Further analysis revealed that EPHB4 forms a ternary complex with VE-PTP and TIE2 in endothelial cells. VE-PTP controls the phosphorylation of each of these two tyrosine kinase receptors. Despite of their simultaneous presence in a ternary complex, stimulating each of the receptors with their own specific ligand did not cross-activate the respective partner receptor. Our systematic approach has led to the identification of novel substrates of VE-PTP, of which many are relevant for the control of cellular junctions further promoting the importance of VE-PTP as a key player of junctional signalling. |
HostingRepository | PRIDE |
AnnounceDate | 2019-08-20 |
AnnouncementXML | Submission_2019-08-20_05:55:41.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Hannes Drexler |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | phosphorylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-12-05 05:58:18 | ID requested | |
⏵ 1 | 2019-08-20 05:55:42 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
curator keyword: Biological |
submitter keyword: mouse, endothelial cells, tyrosine phosphatase, substrate trapping, LC-MSMS |
Contact List
Hannes C. A. Drexler |
contact affiliation | Max Planck Institute for Molecular Biomedicine Bioanalytical Mass Spectrometry Röntgenstr. 20 48149 Münster Germany |
contact email | hannes.drexler@mpi-muenster.mpg.de |
lab head | |
Hannes Drexler |
contact affiliation | Bioanalytical Mass Spectrometry |
contact email | hannes.drexler@mpi-muenster.mpg.de |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD011940
- Label: PRIDE project
- Name: Vascular endothelial protein tyrosine phosphatase: Identification of novel cell junction-related substrates and a ternary receptor complex with EPHB4 and TIE2