Regulation of PTP1B activation through disruption of redox-complex formation

A transient interaction between 14-3-3 zeta and a loop of PTP1B is detected following PTP1B inactivation by reversible oxidation. We have identified a molecular interaction between the reversibly oxidized form of protein tyrosine phosphatase 1B (PTP1B) and 14-3-3 zeta that regulates PTP1B activity. Destabilizing the transient interaction between 14-3-3 zeta and PTP1B prevented PTP1B inactivation by reactive oxygen species and decreased epidermal growth factor receptor phosphorylation. Our data suggest that destabilizing the interaction between 14-3-3 zeta and the reversibly oxidized and inactive form of PTP1B may establish a path to PTP1B activation in cells.