GSK-3? is Dephosphorylated by PP2A in a Leu309 Methylation-Independent Manner.

Hyperphosphorylation of tau is pivotally involved in the pathogenesis of Alzheimer's disease (AD) and related tauopathies. Glycogen synthase kinase-3? (GSK-3?) and protein phosphate 2A (PP2A) are crucial enzymes to regulate tau phosphorylation. GSK-3? activity is regulated by its inhibitory phosphorylation at Ser9. We previously reported the cross-talk between GSK-3? and ...
PP2A signaling and showed that PP2A could dephosphorylate GSK-3? at Ser9. Here, we investigated the dephosphorylation of GSK-3? in brain extracts in the presence of phosphatase inhibitors and found that a PP2A-like phosphatase activity was required for dephosphorylation of GSK-3? at Ser9. PP2A interacted with GSK-3? and suppressed its Ser9 phosphorylation in vitro and in HEK-293FT cells. Activity of PP2A negatively correlated to the level of phosphorylated GSK-3? in kainic acid-induced excitotoxic mouse brain. Alteration of methylation of the catalytic subunit of PP2A (PP2Ac) at Leu309 did not affect GSK-3? phosphorylation. These findings suggest that Leu309 methylation is not required for PP2A to dephosphorylate GSK-3? at Ser9.
Mesh Terms:
Animals, Brain, Carboxylic Ester Hydrolases, Cell Line, Transformed, Dose-Response Relationship, Drug, Enzyme Inhibitors, Excitatory Amino Acid Agonists, Glycogen Synthase Kinase 3, Glycogen Synthase Kinase 3 beta, Humans, Kainic Acid, Leucine, Luminescent Proteins, Male, Methylation, Mice, Phosphorylation, Protein O-Methyltransferase, Protein Phosphatase 2, RNA, Small Interfering, Serine, tau Proteins
J Alzheimers Dis
Date: Oct. 21, 2015
Download Curated Data For This Publication
232173
Switch View:
  • Interactions 3