PXD000462

PXD000462 is an original dataset announced via ProteomeXchange.

Title	VEGF Study in Primary Human Endothelial Cells
Description	The process of angiogenesis is under complex regulation in adult organisms, particularly as it often occurs in an inflammatory post-wound environment. As such, there are many impacting factors that will regulate the generation of new blood vessels which include not only pro-angiogenic growth factors such as vascular endothelial growth factor, but also angiostatic factors. During initial post-wound hemostasis, a large initial bolus of platelet factor 4 is released into localized areas of damage prior to progression of wound healing toward tissue homeostasis. Due to its early presence and high concentration, the angiostatic chemokine platelet factor 4, which can induce endothelial anoikis, can strongly affect angiogenesis. In our work, we explored signaling crosstalk interactions between vascular endothelial growth factor and platelet factor 4 using phosphotyrosine-enriched mass spectrometry methods on human dermal microvascular endothelial cells cultured under conditions facilitating migratory sprouting into collagen gel matrices. We developed new methods to enable mass spectrometry-based phosphorylation analysis of primary cells cultured on collagen gels, and quantified signaling pathways over the first 48 hours of treatment with vascular endothelial growth factor in the presence or absence of platelet factor 4. By observing early and late signaling dynamics in tandem with correlation network modeling, we found that platelet factor 4 has significant crosstalk with vascular endothelial growth factor by modulating cell migration and polarization pathways, centered around P38α MAPK, Src family kinases Fyn and Lyn, along with FAK. Interestingly, we found EphA2 correlational topology to strongly involve key migration-related signaling nodes after introduction of platelet factor 4, indicating an influence of the angiostatic factor on this ambiguous but generally angiogenic signal in this complex environment.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:19:05.813.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nathan Tedford
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; iTRAQ8plex-116 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2013-09-13 01:40:53	ID requested
1	2014-04-15 04:04:46	announced
2	2014-07-24 03:49:42	announced	Updated project metadata.
⏵ 3	2024-10-22 04:19:06	announced	2024-10-22: Updated project metadata.

Hang TC, Tedford NC, Reddy RJ, Rimchala T, Wells A, White FM, Kamm RD, Lauffenburger DA, Vascular endothelial growth factor (VEGF) and platelet (PF-4) factor 4 inputs modulate human microvascular endothelial signaling in a three-dimensional matrix migration context. Mol Cell Proteomics, 12(12):3704-18(2013) [pubmed]

10.1074/mcp.M113.030528;

curator keyword: Biomedical

submitter keyword: Human, LC-MSMS, Angiogenesis, Primary Enodothelial

Nathan Tedford
contact affiliation	Biological Engineering
contact email	ntedford@gmail.com
lab head
Nathan Tedford
contact affiliation	Biological Engineering
contact email	ntedford@gmail.com
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/2014/04/PXD000462

PRIDE project URI

• PRIDE
  1. PXD000462
     1. Label: PRIDE project
     2. Name: VEGF Study in Primary Human Endothelial Cells