PXD010959

PXD010959 is an original dataset announced via ProteomeXchange.

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

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.

10.15252/embr.201847046;

curator keyword: Biological

submitter keyword: junctions, phosphatase, transmigration, signalling,VE-PTP, LC-MSMS, FGD5, shotgun proteomics, inflammation, PTPRB, tyrosine kinase receptor, adhesion, phosphorylation, endothelium

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

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/2019/05/PXD010959

PRIDE project URI

• PRIDE
  1. PXD010959
     1. Label: PRIDE project
     2. Name: VE-PTP inhibition stabilizes endothelial junctions by activating FGD5