PXD010959 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | VE-PTP inhibition stabilizes endothelial junctions by activating FGD5 |
Description | Inhibition of VE-PTP, an endothelial receptor type tyrosine phosphatase, triggers phosphorylation of the tyrosine kinase receptor Tie-2, which leads to the suppression of inflammation-induced vascular permeability. Analyzing the underlying mechanism, we show here that inhibition of VE-PTP and activation of Tie-2 induce tyrosine phosphorylation of FGD5, a GTPase exchange factor (GEF) for Cdc42, and stimulate translocation of this GEF to cell contacts. Interfering with the expression of FGD5 blocked the junction stabilizing effect of VE-PTP inhibition in vitro and in vivo. Likewise, FGD5 was required for strengthening of cortical actin bundles and inhibiting radial stress fiber formation, which were each stimulated by VE-PTP inhibition. We identified Y820 of FGD5 as the direct substrate for VE-PTP. Inhibition of VE-PTP could no longer stabilize endothelial junctions or activate Cdc42 if endothelial cells expressed a Y820F point mutated version of FGD5. In contrast, FGD5-Y820F was still recruited to endothelial cell contacts. Thus, activation of FGD5 is a two-step process that comprises membrane recruitment and phosphorylation of Y820. These steps are necessary for the junction stabilizing effect that is stimulated by VE-PTP inhibition and Tie-2 activation. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_04:07:38.232.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; scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue |
Instrument | LTQ Orbitrap Velos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-08-31 00:03:59 | ID requested | |
1 | 2019-05-04 03:35:52 | announced | |
2 | 2019-05-31 02:23:29 | announced | Updated publication reference for PubMed record(s): 31088862. |
⏵ 3 | 2024-10-22 04:07:39 | announced | 2024-10-22: Updated project metadata. |
Publication List
Keyword List
curator keyword: Biological |
submitter keyword: junctions, phosphatase, transmigration, signalling,VE-PTP, LC-MSMS, FGD5, shotgun proteomics, inflammation, PTPRB, tyrosine kinase receptor, adhesion, phosphorylation, endothelium |
Contact List
Hannes C. A. Drexler |
contact affiliation | Head Bioanalytical Mass Spectrometry; Max Planck Institute for Molecular Biomedicine; Röntgenstr. 20, 48149 Münster, Germany |
contact email | hannes.drexler@mpi-muenster.mpg.de |
lab head | |
Hannes Drexler |
contact affiliation | Bioanalytical Mass Spectrometry, Max Planck Insitute for Molecular Biomedicine, Roentgenstr. 20, 48149 Münster, Germany |
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
- PXD010959
- Label: PRIDE project
- Name: VE-PTP inhibition stabilizes endothelial junctions by activating FGD5