Regulatory B subunits of protein phosphatase 2A are involved in site-specific regulation of tau protein phosphorylation

Un Young Yu, Byong Chul Yoo, Jung Hyuck Ahn

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Overexpression of amyloid precursor protein with the Swedish mutation causes abnormal hyperphosphorylation of the microtubule-associated protein tau. Hyperphosphorylated isoforms of tau are major components of neurofibrillary tangles, which are histopathological hallmarks of Alzheimer's disease. Protein phosphatase 2A (PP2A), a major tau protein phosphatase, consists of a structural A subunit, catalytic C subunit, and a variety of regulatory B subunits. The B subunits have been reported to modulate function of the PP2A holoenzyme by regulating substrate binding, enzyme activity, and subcellular localization. In the current study, we characterized regulatory B subunit-specific regulation of tau protein phosphorylation. We showed that the PP2A B subunit PPP2R2A mediated dephosphorylation of tau protein at Ser-199, Ser-202/Thr-205, Thr-231, Ser-262, and Ser-422. Down-regulation of PPP2R5D expression decreased tau phosphorylation at Ser-202/Thr-205, Thr-231, and Ser-422, which indicates activation of the tau kinase glycogen synthase kinase 3 beta (GSK3β) by PP2A with PPP2R5D subunit. The level of activating phosphorylation of the GSK3β kinase Akt at Thr-308 and Ser-473 were both increased by PPP2R5D knockdown. We also characterized B subunit-specific phosphorylation sites in tau using mass spectrometric analysis. Liquid chromatography-mass spectrometry revealed that the phosphorylation status of the tau protein may be affected by PP2A, depending on the specific B subunits. These studies further our understanding of the function of various B subunits in mediating site-specific regulation of tau protein phosphorylation.

Original languageEnglish
Pages (from-to)155-161
Number of pages7
JournalKorean Journal of Physiology and Pharmacology
Volume18
Issue number2
DOIs
StatePublished - Apr 2014

Keywords

  • Alzheimer's disease
  • Phosphorylation
  • Protein phosphatase 2A
  • Tau protein

Fingerprint

Dive into the research topics of 'Regulatory B subunits of protein phosphatase 2A are involved in site-specific regulation of tau protein phosphorylation'. Together they form a unique fingerprint.

Cite this