Phosphorylation of amyloid-β at the serine 26 residue by human cdc2 kinase

The amyloid-beta (A beta) peptide has been implicated in the pathology of Alzheimer's disease (AD). Using an antisense peptide approach a novel interaction between A beta and the human cdc2 kinase was identified. The A beta 1-42, 1-40 and 25-35 peptides were shown to be substrates for the cdc2 kinase and phosphorylated on the Serine 26 residue. Phosphorylated A beta (pSA beta) was found in extracts from NT-2 neurons and AD brain. In NT-2 neurons the levels of pSA beta were increased in the presence of exogenous A beta and this increase was prevented by a cdc2 protein kinase inhibitor, olomoucine, that also prevented A beta cytotoxicity. The results from this study suggest that A beta phosphorylation by cdc2 could play a role in the brain pathology of AD. NeuroReport 12:3839-3844 (C) 2001 Lippincott Williams & Wilkins.