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PXD044933-1

PXD044933 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitlePAK6-mediated phosphorylation of PPP2R2C regulates LRRK2-PP2A complex formation without affecting PP2A activity.
DescriptionMutations in leucine rich repeat kinase 2 (LRRK2) are a common cause of inherited and sporadic Parkinson’s disease (PD) and previous work suggests that dephosphorylation of LRRK2 at a cluster of heterologous phosphosites is associated to disease. We have previously reported subunits of the PP1 and PP2A classes of phosphatases as well as the PAK6 kinase as regulators of LRRK2 dephosphorylation. We therefore hypothesized that PAK6 may have a functional link with LRRK2’s phosphatases. To investigate this, we used PhosTag with purified proteins and found that PAK6 phosphorylates the PP2A regulatory subunit PPP2R2C at position S381. While S381 phosphorylation did not affect PP2A holoenzyme formation, a S381A phosphodead PPP2R2C showed impaired binding to LRRK2. Also, PAK6 kinase activity changed PPP2R2C subcellular localization in a S381 phosphorylation-dependent manner. Finally, PAK6-mediated dephosphorylation of LRRK2 was unaffected by phosphorylation of PPP2R2C at S381, suggesting that this mechanism is likely subordinate to the previously reported mechanism whereby PAK6-mediated phosphorylation of 14-3-3 proteins promotes 14-3-3-LRRK2 complex dissociation and consequent exposure of LRRK2 phosphosites for dephosphorylation. Taken together, we conclude that PAK6-mediated phosphorylation of PPP2R2C regulates recruitment of PPP2R2C to the LRRK2 complex and PPP2R2C subcellular localization, pointing to an additional mechanism in the fine-tuning of LRRK2 phosphoregulation.
HostingRepositoryPRIDE
AnnounceDate2023-12-06
AnnouncementXMLSubmission_2023-12-06_06:47:17.479.xml
DigitalObjectIdentifierhttps://dx.doi.org/10.6019/PXD044933
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportSupported dataset by repository
PrimarySubmitterSALIOU Jean-Michel
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02023-08-29 06:57:28ID requested
12023-12-06 06:47:17announced
Publication List
10.3389/FNMOL.2023.1269387;
10.6019/PXD044933;
Keyword List
submitter keyword: dephosphorylation, PAK6,LRRK2, PP2A, phosphorylation, PPP2R2C, Parkinson’s disease
Contact List
Jean-Michel Saliou
contact affiliationUniv. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US41 – UAR 2014 – PLBS, F-59000 Lille, France
contact emailjean-michel.saliou@pasteur-lille.fr
lab head
SALIOU Jean-Michel
contact affiliationInstitut Pasteur de Lille
contact emailjean-michel.saliou@pasteur-lille.fr
dataset submitter
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Dataset FTP location
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