REVERSIBLE REGULATION OF SHP-1 TYROSINE PHOSPHATASE-ACTIVITY BY OXIDATION

Increasing evidence indicates that redox regulation is an important si gnaling mechanism. Protein tyrosine phosphatases (PTPases) are sensiti ve to oxidative inactivation and are potential targets of redox regula tion. In this study, we analyzed the reversibility of oxidative inacti vation of the PTPase SHP-1, which negatively regulates protein tyrosin e kinase signaling. H2O2 inactivated SHP-1 in vitro. Incubation of the H2O2-inactivated SHP-1 with dithiothreitol recovered 44-99% of the PT Pase 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.