PXD002665

PXD002665 is an original dataset announced via ProteomeXchange.

Title	Quantitative phosphoproteomics analysis of ERBB3/ERBB4 signaling
Description	The four members of the epidermal growth factor receptor (EGFR/ERBB) family form homo- and heterodimers which mediate ligand-specific regulation of many key cellular processes in normal and cancer tissues. While signaling through the EGFR has been extensively studied on the molecular level, signal transduction through ERBB3/ERBB4 heterodimers is less well understood. Here, we generated isogenic mouse Ba/F3 cells that express full-length and functional membrane-integrated ERBB3 and ERBB4 or ERBB4 alone, to serve as a defined cellular model for biological and phosphoproteomics analysis of ERBB3/ERBB4 signaling. ERBB3 co-expression significantly enhanced Ba/F3 cell proliferation upon neuregulin-1 (NRG1) treatment. For comprehensive signaling studies we performed quantitative mass spectrometry (MS) experiments to compare the basal ERBB3/ERBB4 cell phosphoproteome to NRG1 treatment of ERBB3/ERBB4 and ERBB4 cells. We employed a workflow comprising differential isotope labeling with mTRAQ reagents followed by chromatographic peptide separation and final phosphopeptide enrichment prior to MS analysis. Overall, we identified 9686 phosphorylation sites which could be confidently localized to specific residues. Statistical analysis of three replicate experiments revealed 492 phosphorylation sites which were significantly changed in NRG1-treated ERBB3/ERBB4 cells. Bioinformatics data analysis recapitulated regulation of mitogen-activated protein kinase and Akt pathways, but also indicated signaling links to cytoskeletal functions and nuclear biology. Comparative assessment of NRG1-stimulated ERBB4 Ba/F3 cells indicated that ERBB3 did not trigger defined signaling pathways but more broadly enhanced phosphoproteome regulation in cells expressing both receptors. In conclusion, our data provide the first global picture of ERBB3/ERBB4 signaling and provide numerous potential starting points for further mechanistic studies
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_03:59:05.798.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sebastian Wandinger
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2015-08-04 23:46:43	ID requested
1	2016-01-15 06:37:02	announced
⏵ 2	2024-10-22 03:59:14	announced	2024-10-22: Updated project metadata.

10.1371/journal.pone.0146100;

Wandinger SK, Lahortiga I, Jacobs K, Klammer M, Jordan N, Elschenbroich S, Parade M, Jacoby E, Linders JT, Brehmer D, Cools J, Daub H, Quantitative Phosphoproteomics Analysis of ERBB3/ERBB4 Signaling. PLoS One, 11(1):e0146100(2016) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: ERBB3, ERBB4, phosphoproteomics

Henrik Daub
contact affiliation	Evotec (München) GmbH
contact email	henrik.daub@evotec.com
lab head
Sebastian Wandinger
contact affiliation	Evotec
contact email	sebastian.wandinger@evotec.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/2016/01/PXD002665

PRIDE project URI

• PRIDE
  1. PXD002665
     1. Label: PRIDE project
     2. Name: Quantitative phosphoproteomics analysis of ERBB3/ERBB4 signaling