Effects of Metal Ions on the Activity of Protein Tyrosine Phosphatase VHR: Highly Potent and Reversible Oxidative Inactivation by Cu2+ Ion
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- Effects of Metal Ions on the Activity of Protein Tyrosine Phosphatase VHR: Highly Potent and Reversible Oxidative Inactivation by Cu2+ Ion
- Jin Hahn Kim; Hyeong Jin Cho; Seong Eon Ryu; Myung Un Choi
- Bibliographic Citation
- Archives of Biochemistry and Biophysics, vol. 382, no. 1, pp. 72-80
- Publication Year
- The posttranslational regulation of protein tyrosine phosphatases (PTPs) has been suggested to have a crucial role in maintaining the phosphotyrosine level in cells. Here we examined the regulatory effects of metal ions on human dual-specificity vaccinia H1-related protein tyrosine phosphatase (VHR) in vitro. Among various metal ions examined, Fe3+, Cu2+, Zn2+, and Cd2+ exerted their inactivational effects on VHR, and Cu2+ is the most potent inactivator. The VHR activity inactivated by the metal ions except Cu2+ was significantly restored by EDTA. The efficacy of Cu2+ for the VHR inactivation was about 200-fold more potent than that of H2O2. Cu2+ also inactivated other PTPs including PTPIB and SHP-1. The Cu2+-mediated inactivation at the submicromolar range was eradicated by dithiothreitol treatment. The loss of VHR activity correlated with the decreased [14C]iodoacetate labeling of active-site cysteine, suggesting that Cu2+ brought about the oxidation of the active-site cysteine. On the contrary, Zn2+ that exerted an inactivational effect at millimolar concentrations appeared not directly linked to the active-site cysteine, as indicated by the fact that [14C]iodoacetate labeling was unaffected and that the effect of Zn2+ on the Y78F mutant was increased. The reduction potential of VHR was estimated to be -331 mV by utilizing the reversibility of the redox state of VHR. Thus, we conclude that the highly potent Cu2+ inactivation of VHR is a consequence of the oxidation of the active-site cysteine and the mode of Zn2+ inactivation is distinct from that of Cu2+.
- Copper ion; Metal ions; Oxidative inactivation; Protein tyrosine phosphatase; VHR
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