⮝ Full datasets listing
PXD076579
PXD076579 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Phosphorylation of Phospholamban is Required for a Complete Cellular Adrenergic Response |
| Description | Adrenergic stimulation modulates excitation-contraction coupling (ECC) and cardiac function. The main effector is protein kinase A (PKA), which phosphorylates multiple ECC proteins. Key PKA targets include phospholamban (PLB), a regulator of SERCA2-mediated Ca2+ uptake. Previous studies using transgenic overexpression of non-phosphorylatable PLB reported that Ca2+ release and inotropy were partially preserved in response to adrenergic stimulation, suggesting that PLB phosphorylation might be non-essential; however, this model may be confounded by random transgene insertion and compensatory mechanisms. We used CRISPR/Cas9 to generate a mouse model with genomic mutations resulting in non-phosphorylatable alanine substitutions at S16 and T17 (PLB-DM). Mass spectrometry confirmed the total absence of PLB phosphorylation in PLB-DM hearts. PLB-DM mice had normal heart structure and only exhibited mild bradycardia. In isolated cardiomyocytes, the inotropic and lusitropic responses to isoproterenol were significantly blunted compared to WT controls. PLB-DM myocytes show reduced Ca2+ transient amplitude and decay, and reduced SR Ca2+ load compared to WT controls under isoproterenol stimulation. Calcium current density and kinetics remained unaltered in PLB-DM myocytes, suggesting that previous reports of "preserved" inotropy likely reflected model-specific compensatory adaptations. These results demonstrate that PLB phosphorylation is indispensable for a complete cellular adrenergic response. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-06-22 |
| AnnouncementXML | Submission_2026-06-22_08:24:04.853.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Holden Rogers |
| SpeciesList | scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | Phospho; Acetyl |
| Instrument | impact II; nanoACQUITY UPLC |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2026-04-03 09:36:28 | ID requested | |
| ⏵ 1 | 2026-06-22 08:24:05 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: top-down proteomics, phospholamban, phosphorylation, DatasetType:Proteomics |
Contact List
| Ying Ge | |
|---|---|
| contact affiliation | UW-Madison |
| contact email | ying.ge@wisc.edu |
| lab head | |
| Holden Rogers | |
| contact affiliation | University of Wisconsin-Madison |
| contact email | htrogers@wisc.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| 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://massive-ftp.ucsd.edu/v12/MSV000101353/ |
