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 H(2)O(2) and that this effect is mediated by a c-Abl-dependent mechanism. In concert with these results, we show that H(2)O(2)-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.
Sun
X
X
Dana-Farber Cancer Institute, Harvard Medical School, Boston Massachusetts 02115, USA.
Majumder
P
P
Shioya
H
H
Wu
F
F
Kumar
S
S
Weichselbaum
R
R
Kharbanda
S
S
Kufe
D
D
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D019556:COS Cells; D002467:Cell Nucleus / Q000201:enzymology; D002478:Cells, Cultured; D003593:Cytoplasm / Q000201:enzymology; D004622:Embryo, Mammalian; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D016315:Proto-Oncogene Proteins c-abl / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000502:physiology*
D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D016315:Proto-Oncogene Proteins c-abl; D000111:Acetylcysteine