PXD044933

PXD044933 is an original dataset announced via ProteomeXchange.

Title	PAK6-mediated phosphorylation of PPP2R2C regulates LRRK2-PP2A complex formation without affecting PP2A activity.
Description	Mutations 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.
HostingRepository	PRIDE
AnnounceDate	2023-12-06
AnnouncementXML	Submission_2023-12-06_06:47:17.479.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD044933
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	SALIOU Jean-Michel
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-08-29 06:57:28	ID requested
⏵ 1	2023-12-06 06:47:17	announced

10.3389/FNMOL.2023.1269387;

10.6019/PXD044933;

submitter keyword: dephosphorylation, PAK6,LRRK2, PP2A, phosphorylation, PPP2R2C, Parkinson’s disease

Jean-Michel Saliou
contact affiliation	Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, US41 – UAR 2014 – PLBS, F-59000 Lille, France
contact email	jean-michel.saliou@pasteur-lille.fr
lab head
SALIOU Jean-Michel
contact affiliation	Institut Pasteur de Lille
contact email	jean-michel.saliou@pasteur-lille.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044933
     1. Label: PRIDE project
     2. Name: PAK6-mediated phosphorylation of PPP2R2C regulates LRRK2-PP2A complex formation without affecting PP2A activity.