PXD036506

PXD036506 is an original dataset announced via ProteomeXchange.

Title	Alteration in Tyrosine Phosphorylation of Cardiac Proteome and EGFR Pathway Contribute to Hypertrophic Cardiomyopathy
Description	Alterations of serine/threonine phosphorylation of the cardiac proteome are a hallmark of heart failure. However, the contribution of tyrosine phosphorylation (pTyr) to the pathogenesis of cardiac hypertrophy remains unclear. We use global mapping to discover and quantify site-specific pTyr in two cardiac hypertrophic mouse models, i.e., cardiac overexpression of ErbB2 (TgErbB2) and myosin heavy chain R403Q (R403Q-aMyHC Tg), compared to control hearts. From this, there are significant phosphoproteomic alterations in TgErbB2 mice in right ventricular cardiomyopathy, hypertrophic cardiomyopathy (HCM), and dilated cardiomyopathy (DCM) pathways. On the other hand, R403Q-aMyHC Tg mice indicated that the EGFR1 pathway is central for cardiac hypertrophy, along with angiopoietin, ErbB, growth hormone, and chemokine signaling pathways activation. Surprisingly, most myofilament proteins have downregulation of pTyr rather than upregulation. Kinase-substrate enrichment analysis (KSEA) shows a marked downregulation of MAPK pathway activity downstream of k-Ras in TgErbB2 mice and activation of EGFR, focal adhesion, PDGFR, and actin cytoskeleton pathways. In vivo ErbB2 inhibition by AG-825 decreases cardiomyocyte disarray. Serine/threonine and tyrosine phosphoproteome confirms the above-described pathways and the effectiveness of AG-825 treatment. Thus, altered pTyr may play a regulatory role in cardiac hypertrophic models.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:24:34.125.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Genaro Ramirez-Correa
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-05 08:53:19	ID requested
1	2023-03-10 13:37:20	announced
⏵ 2	2023-11-14 08:24:36	announced	2023-11-14: Updated project metadata.

Xu M, Bermea KC, Ayati M, Kim HB, Yang X, Medina A, Fu Z, Heravi A, Zhang X, Na CH, Everett AD, Gabrielson K, Foster DB, Paolocci N, Murphy AM, Ramirez-Correa GA, Alteration in tyrosine phosphorylation of cardiac proteome and EGFR pathway contribute to hypertrophic cardiomyopathy. Commun Biol, 5(1):1251(2022) [pubmed]

submitter keyword: Heart, tyrosine phosphorylation, proteomics, serine phosphorylation, threonine phosphorylation

Genaro Ramirez Correa
contact affiliation	6Department of Molecular Science/UT Health Rio Grande Valley, USA
contact email	genaro.ramirezcorrea@utrgv.edu
lab head
Genaro Ramirez-Correa
contact affiliation	University of Texas Rio Grande Valley (UTRGV) School of Medicine, Department of Molecular Science
contact email	genaro.ramirezcorrea@utrgv.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/2023/03/PXD036506

PRIDE project URI

• PRIDE
  1. PXD036506
     1. Label: PRIDE project
     2. Name: Alteration in Tyrosine Phosphorylation of Cardiac Proteome and EGFR Pathway Contribute to Hypertrophic Cardiomyopathy