title: Methods to monitor classical protein-tyrosine phosphatase oxidation.
abstract: Reactive oxygen species (ROS), particularly hydrogen peroxide (H(2)O(2)), act as intracellular second messengers in many signaling pathways. Protein-tyrosine phosphatases (PTPs) are now believed to be important targets of ROS. PTPs contain a conserved catalytic cysteine with an unusually low pK(a). This property allows PTPs to execute nucleophilic attack on substrate phosphotyrosyl residues, but also renders them highly susceptible to oxidation. Reversible oxidation, which inactivates PTPs, is emerging as an important cellular regulatory mechanism and might contribute to human diseases, including cancer. Given their potential toxicity, it seems likely that ROS generation is highly controlled within cells to restrict oxidation to those PTPs that must be inactivated for signaling to proceed. Thus, identifying ROS-inactivated PTPs could be tantamount to finding the PTP(s) that critically regulate a specific signaling pathway. This article provides an overview of the methods currently available to identify and quantify PTP oxidation and outlines future challenges in redox signaling.
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, Canada. rkarisch@uhnresearch.ca
authors.forename: Robert
authors.initials: R
authors.lastname: Karisch
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Neel
mesh_terms: D002384:Catalysis; D002623:Chemistry Techniques, Analytical / Q000379:methods; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D007527:Isoenzymes; D017382:Reactive Oxygen Species; D017027:Protein Tyrosine Phosphatases; D003545:Cysteine