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.
Kumar
S
S
Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Pandey
P
P
Bharti
A
A
Jin
S
S
Weichselbaum
R
R
Weaver
D
D
Kufe
D
D
Kharbanda
S
S
D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D006801:Humans; D009687:Nuclear Proteins; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000378:metabolism*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; D019061:src-Family Kinases; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases