Methylation of the C-terminal leucine residue of the PP2A catalytic subunit is unnecessary for the catalytic activity and the binding of regulatory subunit (PR55/B)

Biochem Biophys Res Commun. 2007 Mar 23;354(4):1052-7. doi: 10.1016/j.bbrc.2007.01.085. Epub 2007 Jan 24.


Protein phosphatase 2A (PP2A) is composed of structural (A), catalytic (C), and regulatory (B) subunits. The catalytic subunit (PP2A(C)) undergoes reversible carboxyl-methylation and -demethylation at its C-terminal leucine residue (Leu309), catalyzed by PP2A-methyltransferase (PMT) and PP2A methylesterase (PME-1), respectively. In this study, we observed that the activity of PP2A was largely unaffected by the addition of PME-1, and that the regulatory subunit (PR55/B) could bind demethylated PP2A(D). Furthermore, to study the precise effect of Leu309 demethylation on PP2A activity, we generated two His(8)-tagged mutant versions of PP2A(C) containing an alanine residue in place of Leu309, and a deletion of Leu309. Both recombinant mutants exhibited phosphatase activity. In addition, we demonstrated that both mutants could constitute a holoenzyme with the regulatory A and B subunits. Our collective results indicate that methylation of Leu309 of PP2A(C) is unnecessary for the PP2A activity and the binding of PR55/B.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Carboxylic Ester Hydrolases / antagonists & inhibitors
  • Carboxylic Ester Hydrolases / metabolism
  • Catalysis
  • Holoenzymes / metabolism
  • Humans
  • Leucine / metabolism*
  • Methylation
  • Mutation
  • Okadaic Acid / pharmacology
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Protein Phosphatase 2
  • Recombinant Proteins / metabolism


  • Holoenzymes
  • Recombinant Proteins
  • Okadaic Acid
  • Carboxylic Ester Hydrolases
  • protein phosphatase methylesterase-1
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2
  • Leucine