PXD058709-1

PXD058709 is an original dataset announced via ProteomeXchange.

Title	PP2A-B56alpha is a key determinant of cardiac protein phosphorylation and functional responses to beta-adrenergic signalling
Description	B56alpha is a protein phosphatase 2A (PP2A) regulatory subunit which modulates the heart’s inotropic response to acute beta-adrenergic receptor (beta-AR) stimulation, although knowledge of underlying molecular mechanisms is limited. In this study, mice deficient for B56alpha and wildtype controls received an intraperitoneal injection of isoproterenol (0.1 mg/kg) to activate beta-AR signalling in vivo. Hearts were explanted two minutes post-injection and processed for quantitative phosphoproteomics. We identified >200 proteins that were differentially phosphorylated between genotypes, including 26 hyperphosphorylated proteins harbouring a B56 binding motif (i.e. putative substrates). Gene Ontology enrichment analysis revealed ‘regulation of release of sequestered Ca2+ into cytosol by sarcoplasmic reticulum’, ‘cardiac muscle contraction’ and ‘cardiac muscle hypertrophy’ as key processes likely to be impacted by B56alpha deficiency. In vitro, loss of B56alpha in cardiomyocytes blunted acute isoproterenol-induced increases in intracellular calcium transient amplitude, confirming that B56alpha plays a key role in calcium handling. In vivo, loss of B56alpha protected mice from developing systolic dysfunction in response to sustained isoproterenol infusion (60 mg/kg/day for 14 days), despite comparable increases in heart mass. These findings reaffirm a key role for B56alpha as a mediator of physiologically important cardiac responses to beta-AR stimulation and reveal potential new molecular mechanisms for this regulatory function, including putative cardiac B56alpha substrates.
HostingRepository	PRIDE
AnnounceDate	2025-07-17
AnnouncementXML	Submission_2025-07-17_10:46:37.731.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yanlong Ji
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2024-12-09 17:06:13	ID requested
⏵ 1	2025-07-17 10:46:38	announced

Dataset with its publication pending

submitter keyword: calcium handling, SPEG, CaMKII, phosphoproteomics,phosphatases

Christof Lenz
contact affiliation	Core Facility Proteomics, Department of Clinical Chemistry, University Medical Center Goettingen, Germany
contact email	christof.lenz@med.uni-goettingen.de
lab head
Yanlong Ji
contact affiliation	Max-Planck-Institute for Multidisciplinary Sciences
contact email	yanlong.ji@mpibpc.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD058709
     1. Label: PRIDE project
     2. Name: PP2A-B56alpha is a key determinant of cardiac protein phosphorylation and functional responses to beta-adrenergic signalling