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 numbering). 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 unidentified 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 7,000-fold from rat brain and identified as a approximately 43 kDa protein that is distinct from a number of known protein kinases, including PKC and extracellular signal-regulated kinases (ERKs). The identification of a novel protein kinase that phosphorylates Ser655 will hopefully contribute to our understanding of the metabolism and/or function of APP in the pathogenesis of Alzheimer's disease (AD).
D000544:Alzheimer Disease / Q000201:enzymology / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology; D002852:Chromatography, Ion Exchange; D003593:Cytoplasm / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D012694:Serine / Q000378:metabolism*