Interaction between ATM protein and c-Abl in response to DNA damage.

The gene mutated in the autosomal recessive disorder ataxia telangiectasia (AT), designated ATM (for 'AT mutated'), is a member of a family of phosphatidylinositol-3-kinase-like enzymes that are involved in cell-cycle control, meiotic recombination, telomere length monitoring and DNA-damage response. Previous results have demonstrated that AT cells are hypersensitive to ionizing ...
radiation and are defective at the G1/S checkpoint after radiation damage. Because cells lacking the protein tyrosine kinase c-Abl are also defective in radiation-induced G1 arrest, we investigated the possibility that ATM might interact with c-Abl in response to radiation damage. Here we show that ATM binds c-Abl constitutively in control cells but not in AT cells. Our results demonstrate that the SH3 domain of c-Abl interacts with a DPAPNPPHFP motif (residues 1,373-1,382) of ATM. The results also reveal that radiation-induction of c-Abl tyrosine kinase activity is diminished in AT cells. These findings indicate that ATM is involved in the activation of c-Abl by DNA damage and this interaction may in part mediate radiation-induced G1 arrest.
Mesh Terms:
Ataxia Telangiectasia, Cell Cycle Proteins, Cell Line, Cloning, Molecular, DNA Damage, DNA-Binding Proteins, Enzyme Activation, Protein Binding, Protein-Serine-Threonine Kinases, Proteins, Proto-Oncogene Proteins c-abl, Radiation, Ionizing, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Tumor Suppressor Proteins, src Homology Domains
Nature
Date: May. 29, 1997
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