Physical Interaction between Epidermal Growth Factor Receptor and DNA-dependent Protein Kinase in Mammalian Cells

摘要: Binding of extracellular ligands to epidermal growth factor receptors (EGFR) activate signal transduction pathways associated with cell proliferation, and these events are inhibited by monoclonal antibodies against EGFR. Since efficient DNA repair in actively growing cells may require signaling, it was interest explore any linkage between EGFR-mediated signaling DNA-dependent protein kinase (DNA-PK), an enzyme believed be involved repairing double strand breaks V(D)J recombination. We report that anti-EGFR (mAbs), not EGFR ligands, trigger a specific early physical interaction 350-kDa catalytic subunit or its regulatory heterodimeric complex Ku70/80, variety types, both vivo vitro. Inhibition mAb accompanied reduction the levels DNA-PK activity nuclear fraction. Confocal imaging revealed substantial amount co-localized mAb-treated cells. Anti-EGFR mAb-induced Ku70/80 dependent on presence EGFR, but The retains intrinsic activity. Our findings demonstrate existence novel cellular pathway mammalian involves interactions response inhibition signaling. present observations suggest possible role maintenance DNA-PK, interference possibly result impairment nuclei