PXD048421-1

PXD048421 is an original dataset announced via ProteomeXchange.

Title	PDGFRalpha/beta heterodimer activation negatively affects downstream ERK1/2 signaling and cellular proliferation
Description	The platelet-derived growth factor receptor (PDGFR) family of receptor tyrosine kinases consists of two receptors, PDGFRalpha and PDGFRbeta, that homodimerize and heterodimerize upon ligand binding. Here, we tested the hypothesis that differential internalization and trafficking dynamics of the various PDGFR dimers underlie differences in downstream intracellular signaling and cellular behavior. Using a bimolecular fluorescence complementation approach, we demonstrated that PDGFRalpha/beta heterodimers are rapidly internalized into early endosomes. We showed that PDGFRalpha/beta heterodimer activation does not induce downstream phosphorylation of ERK1/2 and significantly inhibits cell proliferation. Further, we identified MYO1D as a protein that preferentially binds PDGFRalpha/beta heterodimers and demonstrated that knockdown of MYO1D leads to retention of PDGFRalpha/beta heterodimers at the plasma membrane, increased phosphorylation of ERK1/2 and increased cell proliferation. Collectively, our findings impart valuable insight into the molecular mechanisms by which specificity is introduced downstream of PDGFR activation to differentially propagate signaling and generate distinct cellular responses.
HostingRepository	PRIDE
AnnounceDate	2025-04-25
AnnouncementXML	Submission_2025-04-25_09:21:25.921.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Katherine Fantauzzo
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	6x(13)C; 6x(13)C; phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2024-01-10 18:28:13	ID requested
⏵ 1	2025-04-25 09:21:26	announced

Campa, ñ, a MB, Perkins MR, McCabe MC, Neumann A, Larson ED, Fantauzzo KA, heterodimer activation negatively affects downstream ERK1/2 signaling and cellular proliferation. bioRxiv, ():(2023) [pubmed]

10.1101/2023.12.27.573428;

submitter keyword: global proteomics, SILAC,PDGFR, HCC15

Katherine Fantauzzo
contact affiliation	Department of Craniofacial Biology, University of Colorado Anschutz Medical Campus, United States of America
contact email	katherine.fantauzzo@cuanschutz.edu
lab head
Katherine Fantauzzo
contact affiliation	University of Colorado Anschutz Medical Campus
contact email	katherine.fantauzzo@cuanschutz.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/2025/04/PXD048421

PRIDE project URI

• PRIDE
  1. PXD048421
     1. Label: PRIDE project
     2. Name: PDGFRalpha/beta heterodimer activation negatively affects downstream ERK1/2 signaling and cellular proliferation