Regulation of DNA-dependent protein kinase by the Lyn tyrosine kinase.
The Src-like protein-tyrosine kinase Lyn is activated by ionizing radiation and certain other DNA-damaging agents, whereas the DNA-dependent protein kinase (DNA-PK), consisting of the catalytic subunits (DNA-PKcs) and Ku DNA-binding components, requires DNA double-stranded breaks for activation. Here we demonstrate that Lyn associates constitutively with DNA-PKcs. The SH3 domain of ... Lyn interacts directly with DNA-PKcs near a leucine zipper homology domain. We also show that Lyn phosphorylates DNA-PKcs but not Ku in vitro. The interaction between Lyn and DNA-PKcs inhibits DNA-PKcs activity and the ability of DNA-PKcs to form a complex with Ku/DNA. These results support the hypothesis that there are functional interactions between Lyn and DNA-PKcs in the response to DNA damage.
Mesh Terms:
DNA-Activated Protein Kinase, DNA-Binding Proteins, Humans, Nuclear Proteins, Phosphorylation, Precipitin Tests, Protein Binding, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Recombinant Fusion Proteins, Tumor Cells, Cultured, src-Family Kinases
DNA-Activated Protein Kinase, DNA-Binding Proteins, Humans, Nuclear Proteins, Phosphorylation, Precipitin Tests, Protein Binding, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Recombinant Fusion Proteins, Tumor Cells, Cultured, src-Family Kinases
J. Biol. Chem.
Date: Oct. 02, 1998
PubMed ID: 9748231
View in: Pubmed Google Scholar
Download Curated Data For This Publication
5966
Switch View:
- Interactions 1