Functional interaction between the c-Abl and Arg protein-tyrosine kinases in the oxidative stress response.
The Abl family of mammalian nonreceptor tyrosine kinases consists of c-Abl and Arg. Recent work has shown that c-Abl and Arg are activated in the cellular response to oxidative stress. The present studies demonstrate that reactive oxygen species (ROS) induce the formation of c-Abl and Arg heterodimers. The results show ... that the c-Abl SH3 domain binds directly to a proline-rich site (amino acids 567-576) in the Arg C-terminal region. Formation of c-Abl.Arg heterodimers also involves direct binding of the Arg Src homology 3 domain to the C-terminal region of c-Abl. The results further demonstrate that the interaction between c-Abl and Arg involves c-Abl-mediated phosphorylation of Arg. The functional significance of the c-Abl-Arg interaction is supported by the demonstration that both c-Abl and Arg are required for ROS-induced apoptosis. These findings indicate that ROS induce c-Abl.Arg heterodimers and that both c-Abl and Arg are necessary as effectors in the apoptotic response to oxidative stress.
Mesh Terms:
Amino Acid Sequence, Animals, Binding Sites, Breast Neoplasms, Cell Line, Cells, Cultured, Cloning, Molecular, Female, Fibroblasts, Humans, Kinetics, Mice, Oxidative Stress, Peptide Fragments, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-abl, Reactive Oxygen Species, Recombinant Fusion Proteins, Sequence Deletion, Tumor Cells, Cultured, src Homology Domains
Amino Acid Sequence, Animals, Binding Sites, Breast Neoplasms, Cell Line, Cells, Cultured, Cloning, Molecular, Female, Fibroblasts, Humans, Kinetics, Mice, Oxidative Stress, Peptide Fragments, Protein-Tyrosine Kinases, Proto-Oncogene Proteins c-abl, Reactive Oxygen Species, Recombinant Fusion Proteins, Sequence Deletion, Tumor Cells, Cultured, src Homology Domains
J. Biol. Chem.
Date: Apr. 11, 2003
PubMed ID: 12569093
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