Reversible regulation of SHP‐1 tyrosine phosphatase activity by oxidation

摘要: SUMMARY: Increasing evidence indicates that redox regulation is an important signaling mechanism. Protein tyrosine phosphatases (PTPases) are sensitive to oxidative inactivation and potential targets of regulation. In this study, we analyzed the reversibility PTPas SHP-1e whic, h negatively regulates protein kinase signaling. H 2 0 inactivated SHP-1 in vitro. Incubatio -inactivaten thde SHP- 1 with dithiothreitol recovered 44-99% PTPase activity, depending on concentrations used inactivate SHP-1. Glutathione N-acetylcysteine also reactivated H02 -treated Stimulatio. SHPn o-f1-transfected HeLa cells wit 2h rapidl y decreased which was completely reversed within 15 min. Thus, inactivatio SHP-n of1 a reversible process. Key words: SHP-1; phosphatase; oxidation; dithiothreitol; glutathione INTRODUCTION Exposure or other oxidants generally increases phosphorylation activates signal transduction pathways positively regulated by (1-7). A likely mechanism for oxidant-mediated inhibition phosphatase (PTPase) activities (8). contain catalytic cysteine residue PTPases known be (9-11). Inhibition shifts balance phosphorylation-dephosphorylation towards pathways. It has been postulated specific common ligand-independent activation membrane receptor kinases ♦Corresponding author. Fax: (813) 979-6713