Activation of protein phosphatase 2A by the Fe2+/ascorbate system.
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.
Yu
J S
JS
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
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
D005296:Ferrous Compounds; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D001205:Ascorbic Acid