Glutathione Peroxidase 1 Is Regulated by the c-Abl and Arg Tyrosine Kinases

The c-Abl and Arg tyrosine kinases are activated in the cellular response to oxidative stress. The present studies demonstrate that c-Abl and Arg associate with glutathione peroxidase 1 (GPx1) and that this interaction is regulated by intracellular oxidant levels. The c-Abl and Arg SH3 domains bind directly to a proline-rich site in GPx1 at amino acids 132-145. GPx1 also functions as a substrate for c-Abl- and Arg-mediated phosphorylation on Tyr-96. The results further show that c-Abl and Arg stimulate GPx activity and that these kinases contribute to GPx-mediated protection of cells against oxidative stress. Our findings provide the first evidence that GPx1 is regulated by a signaling pathway that is activated in the oxidative stress response.