Glycogen synthase kinase-3β regulates leucine-309 demethylation of protein phosphatase-2A via PPMT1 and PME-1

FEBS Lett. 2012 Jul 30;586(16):2522-8. doi: 10.1016/j.febslet.2012.06.018. Epub 2012 Jun 22.

Abstract

Protein phosphatase-2A (PP2A) activity is significantly suppressed in Alzheimer's disease. We have reported that glycogen synthase kinase-3β (GSK-3β) inhibits PP2A via upregulating the phosphorylation of PP2A catalytic subunit (PP2A(C)). Here we studied the effects of GSK-3β on the inhibitory demethylation of PP2A at leucine-309 (dmL309-PP2A(C)). We found that GSK-3β regulates dmL309-PP2A(C) level by regulating PME-1 and PPMT1. Knockdown of PME-1 or PPMT1 eliminated the effects of GSK-3β on PP2A(C). GSK-3 could negatively regulate PP2A regulatory subunit protein level. We conclude that GSK-3β can inhibit PP2A by increasing the inhibitory L309-demethylation involving upregulation of PME-1 and inhibition of PPMT1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Carboxylic Ester Hydrolases / metabolism*
  • Catalysis
  • Cell Line, Tumor
  • DNA Methylation
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Gene Expression Regulation, Enzymologic
  • Glycogen Synthase Kinase 3 / metabolism*
  • Glycogen Synthase Kinase 3 beta
  • HEK293 Cells
  • Humans
  • Lentivirus / genetics
  • Leucine / chemistry*
  • Methylation
  • Protein O-Methyltransferase / metabolism
  • Protein Phosphatase 2 / chemistry*

Substances

  • Enzyme Inhibitors
  • LCMT1 protein, human
  • Protein O-Methyltransferase
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3
  • Carboxylic Ester Hydrolases
  • protein phosphatase methylesterase-1
  • Protein Phosphatase 2
  • Leucine