Phosphorylation of the cytoplasmic domain of Alzheimer's beta-amyloid precursor protein at Ser655 by a novel protein kinase

The cytoplasmic domain of Alzheimer's beta-amyloid precursor protein (APP) can be phosphorylated at Thr654, Ser655, and Thr668 (APP695 isoform numberi ng). Previous studies demonstrated that Ser655 of APP was phosphorylated by protein kinase C (PKC) and calmodulin-dependent protein kinase II (CaMKII) in vitro and by unidentifed protein kinase(s) in vivo. We report here the characterization of a novel protein kinase (designated APP kinase I) which phosphorylates Ser655 of APP, APP kinase I was partially purified over 7,00 0-fold from rat brain and identified as a similar to 43 kDa protein that is distinct from a number of known protein kinases, including PKC and extrace llular signal-regulated kinases (ERKs), The identification of a novel prote in kinase that phosphorylates Ser655 will hopefully contribute to our under standing of the metabolism and/or function of APP in the pathogenesis of Al lzheimer's disease (AD), (C) 1999 Academic Press.