Phosphorylation of protein tau by double-stranded DNA-dependent protein kinase

Alzheimer Disease (AD) is a distinct form of dementia characterized by the occurrence of neurofibrillary tangles, neurotic plaques and loss of certain neuronal populations. The tangles are associated with the presence of abnormal proteinaceous deposits. One such protein, referred to as tau, is found to be excessively phosphorylated in AD. We demonstrate that a double-stranded DNA-stimulated protein kinase (referred to as DNA-PK) effectively catalyzes the phosphorylation of recombinant human protein tau. Moreover, in the presence of stimulatory DNA, the hyperphosphorylation of tau is accompanied by a significant shift in its mobility on SDS polyacrylamide gels. These results suggest that DNA-PK may contribute to the pathogenesis of AD.