title: Regulation of DNA-dependent protein kinase by the Lyn tyrosine kinase.
abstract: 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.
authors.affiliation: Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: S
authors.initials: S
authors.lastname: Kumar
authors.forename: P
authors.initials: P
authors.lastname: Pandey
authors.forename: A
authors.initials: A
authors.lastname: Bharti
authors.forename: S
authors.initials: S
authors.lastname: Jin
authors.forename: R
authors.initials: R
authors.lastname: Weichselbaum
authors.forename: D
authors.initials: D
authors.lastname: Weaver
authors.forename: D
authors.initials: D
authors.lastname: Kufe
authors.forename: S
authors.initials: S
authors.lastname: Kharbanda
mesh_terms: 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*
chemical_list: 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