Phenylarsine Oxide Binding Reveals Redox-Active and Potential Regulatory Vicinal Thiols on the Catalytic Subunit of Protein Phosphatase 2A |
| |
Authors: | Timothy D Foley Scott L Melideo Adriana E Healey Eugene J Lucas Jason A Koval |
| |
Institution: | (1) Department of Chemistry and Program in Biochemistry, Cell, and Molecular Biology, University of Scranton, 800 Linden St., Scranton, PA 18510, USA |
| |
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: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|