A novel redox-based switch: LMW-PTP oxidation enhances Grb2 binding and leads to ERK activation.

A novel redox-based switch: LMW-PTP oxidation enhances Grb2 binding and leads to ERK activation. Giannoni E, Raugei G, Chiarugi P, Ramponi G. Source Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy. Abstract Low molecular weight-PTP has been reported as a redox-sensitive protein during both platelet-derived growth factor and integrin signalling. In response to oxidation the phosphatase undergoes a reversible inactivation, which in turn leads to the increase in tyrosine phosphorylation of its substrates and the properly executed anchorage-dependent proliferation program. Here, we report that an exogenous oxidative stress enhances LMW-PTP tyrosine phosphorylation, through oxidation/inactivation of the enzyme, thus preventing its auto-dephosphorylation activity. In particular, we observed a selective hyper-phosphorylation of Tyr132, that acts as a docking site for the adaptor protein Grb2. The redox-dependent enhancement of Grb2 recruitment to LMW-PTP ultimately leads to an improvement of ERK activation, likely triggering a prosurvival signal against the oxidant environment.