A novel redox-based switch: LMW-PTP oxidation enhances Grb2 binding and leads to ERK activation.
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.
Giannoni
Elisa
E
Department of Biochemical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy.
Raugei
Giovanni
G
Chiarugi
Paola
P
Ramponi
Giampietro
G
D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D051380:GRB2 Adaptor Protein / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells / Q000528:radiation effects; D010084:Oxidation-Reduction; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism; D014466:Ultraviolet Rays
D051380:GRB2 Adaptor Protein; D007527:Isoenzymes; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D017382:Reactive Oxygen Species; D014443:Tyrosine; D048049:Extracellular Signal-Regulated MAP Kinases; C490428:Acp1 protein, mouse; D017027:Protein Tyrosine Phosphatases