PXD012629-1

PXD012629 is an original dataset announced via ProteomeXchange.

Title	VEGFR N-glycosylation .
Description	Vascular endothelial growth factor receptor-2 (VEGFR2) is a highly N-glycosylated receptor tyrosine kinase involved in pro-angiogenic signaling in physiological and pathological contexts, including cancer. VEGFR2 post-translational modifications (PTMs) and their roles in receptor function and signaling have been extensively studied. However, until recently, co- and post-translational N-glycosylation of RTKs has been regarded as decorative rather than functional. N-glycosylation is a non-template based process that generates heterogeneously modified proteins. Emerging evidence suggests that the tumor microenvironment modulates expression of glycosyltransferases involved in the trimming and remodeling of nascent N-linked glycans into their heterogeneous mature forms, and that these changes alter the functions of modified proteins and thereby impact cellular signaling and adhesion. We sought to understand the consequences of altered glycosylation on VEGFR2 signaling. We used multiple strategies, including: enzymatic removal of N-linked glycans from the receptor, site-directed mutagenesis of specific N-glycosylation sites near the VEGF ligand binding site of VEGFR2, mass spectrometry of VEGFR2 glycopeptides, and concurrent measurement of receptor activation, signaling, and dimerization to interrogate how N-glycosylation modulates VEGFR2 ligand-dependent pro-angiogenic signaling. We demonstrate that VEGFR2 glycosylation at site N247 regulates ligand-dependent receptor activation and signaling. Complex N-glycans with α2-6 linked sialic acid residues at site N247 hinder receptor activation, while asialo-glycans favor VEGFR2 ligand-mediated activation and signaling.
HostingRepository	PRIDE
AnnounceDate	2024-10-07
AnnouncementXML	Submission_2024-10-07_10:23:33.754.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Kevin Chandler
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2019-02-08 02:31:35	ID requested
⏵ 1	2024-10-07 10:23:34	announced

10.1074/jbc.ra119.008643;

Chandler KB, Leon DR, Kuang J, Meyer RD, Rahimi N, Costello CE, -Glycosylation regulates ligand-dependent activation and signaling of vascular endothelial growth factor receptor 2 (VEGFR2). J Biol Chem, 294(35):13117-13130(2019) [pubmed]

submitter keyword: VEGFR2, RTK, N-glycosylation, nLC-MS/MS, mouse, glycopeptides

Catherine E Costello
contact affiliation	Center for Biomedical Mass Spectrometry, Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA
contact email	cecmsms@bu.edu
lab head
Kevin Chandler
contact affiliation	Boston University
contact email	kbc36@bu.edu
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/2021/09/PXD012629

PRIDE project URI

• PRIDE
  1. PXD012629
     1. Label: PRIDE project
     2. Name: VEGFR N-glycosylation