Altered phosphorylation of cytoskeletal proteins in mutant protein phosphatase 2A transgenic mice

Andreas Schild, Lars M. Ittner, Jürgen Götz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

Protein phosphatase 2A (PP2A) is a family of heterotrimeric enzymes with diverse functions under physiologic and pathologic conditions such as Alzheimer's disease. All PP2A holoenzymes have in common a catalytic subunit C and a structural scaffolding subunit A. These core subunits assemble with various regulatory B subunits to form heterotrimers with distinct functions in the cell. Substrate specificity of PP2A in vitro is determined by regulatory subunits with leucine 309 of the catalytic subunit C playing a crucial role in the recruitment of regulatory subunits into the complex. Here we expressed a mutant form of Cα, L309A, in brain and Harderian (lacrimal) gland of transgenic mice. We found an altered recruitment of regulatory subunits into the complex, demonstrating a role for the carboxyterminal leucine of Cα in regulating holoenzyme assembly in vivo. This was associated with an increased phosphorylation of tau in brain and an impaired dephosphorylation of vimentin demonstrating that both cytoskeletal proteins are in vivo substrates of distinct PP2A holoenzyme complexes.

Original languageEnglish
Pages (from-to)1171-1178
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume343
Issue number4
DOIs
Publication statusPublished - 19 May 2006
Externally publishedYes

Keywords

  • Alzheimer's disease
  • Okadaic acid
  • Phosphorylation
  • Protein phosphatase 2A
  • Tau
  • Vimentin

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