p(HGNC:PPP2CA, pmod(Me))

Entity

Name

PPP2CA

Namespace

hgnc

Namespace Version

20180906

Namespace URL

https://raw.githubusercontent.com/pharmacome/terminology/b46b65c3da259b6e86026514dfececab7c22a11b/external/hgnc-names.belns

Tau Modifications Sections of NESTOR

Incubation of human SH-SY5Y neuroblastoma cells for 2 h with L-dopa induced a dose-dependent decrease in both soluble and insoluble methylated PP2A C subunit levels, and concomitant accumulation of demethylated PP2A enzymes PubMed:22764226

Significantly, we found similar effects in human dopaminergic neurons (Fig. 2F). Treatment of neurons with L-Dopa induced a 40–49% decrease in methylated PP2A and concomitant 168–179% increase in endogenous p-Tau (PHF-1) levels (Fig. 2G). PubMed:22764226

These findings suggest a scenario in which MC-LR-mediated demethylation of PP2Ac is associated with GSK-3β phosphorylation at Ser9 and contributes to dissociation of Bα from PP2Ac, which would result in Bα degradation and disruption of PP2A/Bα-tau interactions, thus promoting tau hyperphosphorylation and paired helical filaments-tau accumulation and, consequently, axonal degeneration and cell death. PubMed:29228318

These findings suggest a scenario in which MC-LR-mediated demethylation of PP2Ac is associated with GSK-3β phosphorylation at Ser9 and contributes to dissociation of Bα from PP2Ac, which would result in Bα degradation and disruption of PP2A/Bα-tau interactions, thus promoting tau hyperphosphorylation and paired helical filaments-tau accumulation and, consequently, axonal degeneration and cell death. PubMed:29228318

Intriguingly, changes in this peptide motif also affected interaction of the catalytic subunit with the alpha4 protein (α4), presumably through alteration of methylation[ 29], and led to a complex with distinct substrate specificity that is essential for cell survival PubMed:19277525

By contrast, several recent studies using purified, recombinant proteins showed that the methylation status of the catalytic subunit did not play a decisive role for the in vitro assembly of PP2A holoenzymes involving the B and B′ subunit PubMed:19277525

By contrast, several recent studies using purified, recombinant proteins showed that the methylation status of the catalytic subunit did not play a decisive role for the in vitro assembly of PP2A holoenzymes involving the B and B′ subunit PubMed:19277525