Binding of Ku and c-Abl at the kinase homology region of DNA-dependent protein kinase catalytic subunit.
The DNA-dependent protein kinase (DNA-PK) controls the repair of double-stranded DNA breaks in mammalian cells. The protein kinase subunit of DNA-PK (DNA-PKcs) is targeted to DNA breaks by association with the Ku DNA-binding heterodimer. Here we show that a Ku association site is present at the carboxyl terminus of DNA-PKcs ... (amino acids 3002-3850) near the protein kinase domain. Correspondingly, the nuclear c-Abl tyrosine kinase that associates with DNA-PK also binds to the kinase homology domain. The c-Abl SH3 domain binds to amino acids 3414-3850 of DNA-PKcs. c-Abl phosphorylates C-terminal fragments of DNA-PKcs, particularly amino acids 3414-3850. c-Abl phosphorylation of DNA-PKcs disassociates the DNA-PKcs.Ku complex. Thus, Ku and c-Abl provide opposing functions with regard to DNA-PK activity.
Mesh Terms:
Animals, Antigens, Nuclear, B-Lymphocytes, Base Sequence, Binding Sites, Cell Line, DNA Helicases, DNA-Activated Protein Kinase, DNA-Binding Proteins, Dimerization, Gene Library, Glutathione Transferase, Humans, Macromolecular Substances, Mice, Molecular Sequence Data, Nuclear Proteins, Protein Biosynthesis, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins c-abl, Recombinant Fusion Proteins, Transcription, Genetic, Transfection, src Homology Domains
Animals, Antigens, Nuclear, B-Lymphocytes, Base Sequence, Binding Sites, Cell Line, DNA Helicases, DNA-Activated Protein Kinase, DNA-Binding Proteins, Dimerization, Gene Library, Glutathione Transferase, Humans, Macromolecular Substances, Mice, Molecular Sequence Data, Nuclear Proteins, Protein Biosynthesis, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins c-abl, Recombinant Fusion Proteins, Transcription, Genetic, Transfection, src Homology Domains
J. Biol. Chem.
Date: Oct. 03, 1997
PubMed ID: 9312071
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