Regulation of protein tyrosine phosphatase oxidation in cell adhesion and migration

Redox-regulated control of protein tyrosine phosphatases (PTPs) through inhibitory reversible oxidation of their active site is emerging as a novel and general mechanism for control of cell surface receptor-activated signaling. This mechanism allows for a previously unrecognized crosstalk between redox regulators and signaling pathways, governed by, for example, receptor tyrosine kinases and integrins, which control cell proliferation and migration.

A large number of different molecules, in addition to hydrogen peroxide, have been found to induce PTP inactivation, including lipid peroxides, reactive nitrogen species, and hydrogen sulfide. Characterization of oxidized PTPs has identified different types of oxidative modifications that are likely to display differential sensitivity to various reducing systems. Accumulating evidence demonstrates that PTP oxidation occurs in a temporally and spatially restricted manner. Studies in cell and animal models indicate altered PTP oxidation in models of common diseases, such as cancer and metabolic/cardiovascular disease. Novel methods have appeared that allow characterization of global PTP oxidation.

As the understanding of the molecular and cellular biology of PTP oxidation is developing, it will be important to establish experimental procedures that allow analyses of PTP oxidation, and its regulation, in physiological and pathophysiological settings. Future studies should also aim to establish specific connections between various oxidants, specific PTPs, and defined signaling contexts.

Modulation of PTP activity still appears as a valid strategy for correction or inhibition of dys-regulated cell signaling. Continued studies on PTP oxidation might present yet unrecognized means to exploit this regulatory mechanism for pharmacological purposes.