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.
Cao
Cheng
C
Beijing Institute of Biotechnology, Beijing 100850, China.
Leng
Yumei
Y
Li
Chufang
C
Kufe
Donald
D
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001943:Breast Neoplasms; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D005260:Female; D005347:Fibroblasts / Q000502:physiology; D006801:Humans; D007700:Kinetics; D051379:Mice; D018384:Oxidative Stress / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017384:Sequence Deletion; D014407:Tumor Cells, Cultured; D018909:src Homology Domains
D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; C426236:ARG tyrosine kinase; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl