title: Interaction between ATM protein and c-Abl in response to DNA damage.
abstract: 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.
authors.affiliation: Joint Center for Radiation Therapy, Dana Farber Cancer Institutes, Boston, Massachusetts 02115, USA.
authors.forename: T
authors.initials: T
authors.lastname: Shafman
authors.forename: K K
authors.initials: KK
authors.lastname: Khanna
authors.forename: P
authors.initials: P
authors.lastname: Kedar
authors.forename: K
authors.initials: K
authors.lastname: Spring
authors.forename: S
authors.initials: S
authors.lastname: Kozlov
authors.forename: T
authors.initials: T
authors.lastname: Yen
authors.forename: K
authors.initials: K
authors.lastname: Hobson
authors.forename: M
authors.initials: M
authors.lastname: Gatei
authors.forename: N
authors.initials: N
authors.lastname: Zhang
authors.forename: D
authors.initials: D
authors.lastname: Watters
authors.forename: M
authors.initials: M
authors.lastname: Egerton
authors.forename: Y
authors.initials: Y
authors.lastname: Shiloh
authors.forename: S
authors.initials: S
authors.lastname: Kharbanda
authors.forename: D
authors.initials: D
authors.lastname: Kufe
authors.forename: M F
authors.initials: MF
authors.lastname: Lavin
mesh_terms: D001260:Ataxia Telangiectasia / Q000378:metabolism*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002460:Cell Line; D003001:Cloning, Molecular; D004249:DNA Damage; D004268:DNA-Binding Proteins; D004789:Enzyme Activation / Q000528:radiation effects; D011485:Protein Binding / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D011839:Radiation, Ionizing; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D025521:Tumor Suppressor Proteins; D018909:src Homology Domains
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins; D016315:Proto-Oncogene Proteins c-abl; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases