title: Activation of protein phosphatase 2A by the Fe2+/ascorbate system.
abstract: Freshly isolated protein phosphatase 2A (PP2A) was highly active as to the dephosphorylation of protein substrates, but lost most of its spontaneous activity on prolonged storage, and was converted to a latent form requiring Mn2+ or Co2+ ions for activity. In this report, we show that the latent form of PP2A can be activated by the Fe2+/ascorbate system. Activation of the phosphatase required both Fe2+ ions and ascorbate, and the level of activation was dependent on the concentrations of both Fe2+ ions and ascorbate. Both the holoenzyme and catalytic subunit of phosphatase 2A could be activated by the Fe2+/ascorbate system, indicating that direct modulation of the catalytic subunit of the phosphatase by the Fe2+/ascorbate system may cause this activation. Several common divalent metal ions, including Ca2+, Mg2+, Cu2+, Zn2+, and Ni2+ ions, cannot cooperate with ascorbate to activate the phosphatase. Dithiothreitol, a SH-containing reducing agent, could replace ascorbate in the Fe2+/ascorbate system to activate the phosphatase, whereas H2O2, a strong oxidizer, significantly diminished the phosphatase activation by the Fe2+/ascorbate system. The results indicate that iron ions stabilized in the +2 state by reducing agents can activate the phosphatase. Overall, the present study provides initial biochemical evidence suggesting that Fe2+ could be a biologically important metal ion cofactor responsible for PP2A activation.
authors.affiliation: Department of Cell and Molecular Biology, Institute of Basic Medicine, Medical College of Chang Gung University, Tao-Yuan, Taiwan, Republic of China. yusong@mail.cgu.edu.tw
authors.forename: J S
authors.initials: JS
authors.lastname: Yu
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism*; D004789:Enzyme Activation; D005296:Ferrous Compounds / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D054648:Protein Phosphatase 2; D011817:Rabbits; D013552:Swine
chemical_list: D005296:Ferrous Compounds; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D001205:Ascorbic Acid