Phenylarsine Oxide Binding Reveals Redox-Active and Potential Regulatory Vicinal Thiols on the Catalytic Subunit of Protein Phosphatase 2A
- 16 November 2010
- journal article
- research article
- Published by Springer Science and Business Media LLC in Neurochemical Research
- Vol. 36 (2), 232-240
- https://doi.org/10.1007/s11064-010-0310-4
Abstract
Our earlier finding that the activity of protein phosphatase 2A from rat brain is inhibited by micromolar concentrations of the dithiol cross-linking reagent phenylarsine oxide (PAO) has encouraged the hypothesis that the catalytic subunit (PP2Ac) of PP2A contains one or more pairs of closely-spaced (vicinal) thiol pairs that may contribute to regulation of the enzyme. The results of the present study demonstrate using immobilized PAO-affinity chromatography that PP2Ac from rat brain formed stable DTT-sensitive adducts with PAO with or without associated regulatory subunits. In addition, a subset of the PAO-binding vicinal thiols of PP2Ac was readily oxidized to disulfide bonds in vitro. Importantly, a small fraction of PP2Ac was still found to contain disulfide bonds after applying stringent conditions designed to prevent protein disulfide bond formation during homogenization and fractionation of the brains. These findings establish the presence of potentially regulatory and redox-active PAO-binding vicinal thiols on the catalytic subunit of PP2A and suggest that a population of PP2Ac may contain disulfide bonds in vivo.Keywords
This publication has 33 references indexed in Scilit:
- Selective Inhibition of Mitogen-Activated Protein Kinase Phosphatases by Zinc Accounts for Extracellular Signal-Regulated Kinase 1/2-Dependent Oxidative Neuronal Cell DeathMolecular Pharmacology, 2008
- The 3D Structure of Protein Phosphatase 2A: New Insights into a Ubiquitous Regulator of Cell SignalingACS Chemical Biology, 2007
- Inhibition of Protein Phosphatase 2A Activity by Selective Electrophile Alkylation DamageBiochemistry, 2006
- Interaction of nucleoredoxin with protein phosphatase 2AFEBS Letters, 2006
- Brain PP2A is modified by thiol-disulfide exchange and intermolecular disulfide formationBiochemical and Biophysical Research Communications, 2005
- Identification and H2O2 sensitivity of the major constitutive MAPK phosphatase from rat brainBiochemical and Biophysical Research Communications, 2004
- Protein Phosphatase 2A Dephosphorylation of Phosphoserine 112 Plays the Gatekeeper Role for BAD-Mediated ApoptosisMolecular and Cellular Biology, 2003
- Regulation of protein phosphatase 2A by hydrogen peroxide and glutathionylationBiochemical and Biophysical Research Communications, 2002
- Tissue‐specific expression of mRNAs encoding α‐ and β‐catalytic subunits of protein phosphatase 2AFEBS Letters, 1988
- Isolation and sequence analysis of a cDNA clone encoding the entire catalytic subunit of a type‐2A protein phosphataseFEBS Letters, 1987