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.
Cunnick
J M
JM
Molecular Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Dorsey
J F
JF
Mei
L
L
Wu
J
J
D000111:Acetylcysteine / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005978:Glutathione / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D010084:Oxidation-Reduction; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D014162:Transfection; D018909:src Homology Domains
D047908:Intracellular Signaling Peptides and Proteins; D011993:Recombinant Fusion Proteins; D006861:Hydrogen Peroxide; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D005978:Glutathione; D004229:Dithiothreitol; D000111:Acetylcysteine