⮝ Full datasets listing
PXD059469
PXD059469 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Selective knockout of PKA regulatory subunits reveal opposite catalytic and metabolic consequences with implications for Alzheimer's disease |
| Description | cAMP-dependent Protein Kinase A (PKA) is a master regulator of cell signaling involved in energy metabolism, synaptic plasticity, and stress response. Dysregulated PKA signaling is implicated in diseases including neurodegeneration and cancer. PKA catalytic activity is regulated by two nonredundant regulatory subunits, Type I (RI?/RI?) and Type II (RII?/RII?), whose divergent functions are not fully understood. We generated double-knockout (KO) cell lines of RI?/RI? and RII?/RII? subunits and performed multiplexed MS-based proteomic and phosphoproteomic profiling under basal and glucose-perturbed conditions. We found that RI and RII loss drives distinct, and often opposite, remodeling of the cellular proteome and phosphoproteome. While both mutants blunted metabolic flexibility to glycolytic stressors and stimuli, RI and RII KO cells exhibited elevated and depressed glycolytic signaling, respectively. Interestingly, RI KO increased the abundance and kinase activity of the PKA catalytic subunit C? isoform, leading to an increase in PKA substrate phosphorylation, whereas RII KO decreased the abundance, kinase activity, and substrate phosphorylation by the catalytic subunit C? isoform. Notably, one of the most differentially affected PKA sites between RI and RII KOs maps to Tau, whose hyperphosphorylation is a hallmark of Alzheimer’s disease. Loss of RI increased Tau phosphorylation, which was not only caused by increased PKA catalytic activity, but also a higher binding affinity of Tau to RII subunits on the negatively-charged flexible linker region. Overall, the present study demonstrates that PKA RI and RII subunits play nonredundant roles in modulating PKA activity, metabolic flexibility, and phospho-regulation of key disease-associated substrates such as Tau. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-06-30 |
| AnnouncementXML | Submission_2026-06-30_12:46:01.625.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Supported dataset by repository |
| PrimarySubmitter | David Gonzalez |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | TMT6plex; Carbamidomethyl; Oxidation; Phospho |
| Instrument | Orbitrap Fusion |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-01-06 11:00:21 | ID requested | |
| ⏵ 1 | 2026-06-30 12:46:02 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: phosphoproteomics, proteomics, quantitative, knockout, cells, mice, Alzheimer's Disease, protein kinase A, kinase, DatasetType:Proteomics |
Contact List
| David Gonzalez | |
|---|---|
| contact affiliation | UCSD |
| contact email | djgonzalez@ucsd.edu |
| lab head | |
| David Gonzalez | |
| contact affiliation | UCSD |
| contact email | gozolabucsd@gmail.com |
| 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/v06/MSV000096782/ |
