Reversible regulation of SHP-1 tyrosine phosphatase activity by oxidation

Increasing evidence indicates that redox regulation is an important signaling mechanism. Protein tyrosine phosphatases (PTPases) are sensitive to oxidative inactivation and are potential targets of redox regulation. In this study, we analyzed the reversibility of oxidative inactivation of the PTPase SHP-1, which negatively regulates protein tyrosine kinase signaling. H₂O₂ inactivated SHP-1 in vitro. Incubation of the H₂O₂-inactivated SHP-1 with dithiothreitol recovered 44-99% of the PTPase activity, depending on the H₂O₂ concentrations used to inactivate SHP-1. Glutathione and N-acetylcysteine also reactivated H₂O₂-treated SHP-1. Stimulation of SHP-1-transfected HeLa cells with H₂O₂ rapidly decreased SHP-1 activity, which was completely reversed within 15 min. Thus, oxidative inactivation of SHP-1 is a reversible process.