Activation of the cytoplasmic c-Abl tyrosine kinase by reactive oxygen species

The ubiquitously expressed c-Abl protein tyrosine kinase localizes to both the nucleus and cytoplasm. The nuclear form of c-Abl is activated in the cellular response to genotoxic stress. Here we show that cytoplasmic c-Abl is activated by oxidative stress, The results also demonstrate that mitochondrial cytochrome c is released in the cellular response to H2O2 and that this effect is mediated by a c-Abl-dependent mechanism. In concert with these results, we show that H2O2-induced apoptosis is attenuated in c-Abl-deficient cells. These findings demonstrate that cytoplasmic c-Abl is involved in the apoptotic response of cells to oxidative stress.