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PXD010959

PXD010959 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleVE-PTP inhibition stabilizes endothelial junctions by activating FGD5
DescriptionInhibition 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:07:38.232.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHannes Drexler
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListmonohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-08-31 00:03:59ID requested
12019-05-04 03:35:52announced
22019-05-31 02:23:29announcedUpdated publication reference for PubMed record(s): 31088862.
32024-10-22 04:07:39announced2024-10-22: Updated project metadata.
Publication List
10.15252/embr.201847046;
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 affiliationHead Bioanalytical Mass Spectrometry; Max Planck Institute for Molecular Biomedicine; Röntgenstr. 20, 48149 Münster, Germany
contact emailhannes.drexler@mpi-muenster.mpg.de
lab head
Hannes Drexler
contact affiliationBioanalytical Mass Spectrometry, Max Planck Insitute for Molecular Biomedicine, Roentgenstr. 20, 48149 Münster, Germany
contact emailhannes.drexler@mpi-muenster.mpg.de
dataset submitter
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