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PXD004810 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleGlobal phosphoproteomic profiling reveals perturbed signaling in a mouse model of dilated cardiomyopathy
DescriptionProject Description(50 to 5000 characters):Phospholamban (PLN) plays a central role in Ca2+ homeostasis in cardiac myocytes through its regulation of the SERCA2A Ca2+ pump. An inherited mutation converting arginine residue 9 in PLN to cysteine (R9C) results in dilated cardiomyopathy (DCM) in both humans and transgenic mice, but the downstream signaling defects leading to heart failure are poorly understood. Here, we used precision tandem mass spectrometry to gain unbiased insights into the global phosphorylation dynamics of 2041 cardiac phosphoproteins in early affected heart tissue in the transgenic R9C mouse model of DCM compared to wild type littermates. 251 dysregulated phosphorylation sites were quantified after affinity capture and identification of 4337 phosphopeptides from fractionated whole heart homogenates. Enrichment analysis of the differential phosphoprotein patterns revealed dozens of signaling pathways regulating cardiovascular activity that are selectively impaired in early stages of DCM. Strikingly, dysregulated signaling through the Notch-1 receptor, recently linked to cardiomyogenesis and embryonic cardiac stem cell development and differentiation but never directly implicated in DCM before, was one of the most prominently perturbed pathways. We verified dysregulation of Notch1 downstream components in early symptomatic R9C transgenic mouse hearts compared to wild type by immunoblot analysis and confocal immunofluorescence microscopy. These data reveal unexpected connections between protein kinases, cell signaling networks and downstream effectors essential for proper cardiac function
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSadhna Phanse
SpeciesList scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationListphosphorylated residue
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02016-08-15 06:43:39ID requested
12016-12-12 13:05:08announced
22017-10-24 02:18:44announcedUpdated project metadata.
Publication List
Kuzmanov U, Guo H, Buchsbaum D, Cosme J, Abbasi C, Isserlin R, Sharma P, Gramolini AO, Emili A, Global phosphoproteomic profiling reveals perturbed signaling in a mouse model of dilated cardiomyopathy. Proc Natl Acad Sci U S A, 113(44):12592-12597(2016) [pubmed]
Keyword List
curator keyword: Biological, Biomedical
submitter keyword: phosphoproteomics, dialted cardiomyopathy, signaling pathways, Notch, heart failure
Contact List
Andrew Emili
contact affiliationDonnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto ON M5S 3E1, Canada
contact emailandrew.emili@utoronto.ca
lab head
Sadhna Phanse
contact affiliationUniversity of Toronto
contact emailsadhna.phanse@utoronto.ca
dataset submitter
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