Oxidative modification of protein tyrosine phosphatases.

Our understanding of the biological effects of reactive oxidants has deepened considerably over the past decade. Less the indiscriminate loose cannons we previously imagined, both superoxide and hydrogen peroxide appear to target relatively specific molecular structures. Perhaps the most consequential of such targets within proteins is the reduced sulfhydryl of cysteine residues. Because protein tyrosine phosphatases (PTPs) all harbor an absolutely conserved catalytic cysteine residue, oxidation of this residue inactivates PTPs, rendering tyrosine kinase signaling pathways highly sensitive to the local redox environment. Therefore, tyrosine phosphorylation-dependent signaling involving receptor tyrosine kinases, mitogen-activated protein kinases, Abl, Src, and Pyk2 is known to be initiated or amplified by reactive oxidants. We describe a nonradioisotopic method that discriminates between reduced and oxidatively modified tyrosine phosphatases, thus facilitating studies that may mechanistically link oxidant activity with specific signaling pathways.