title: Protein phosphorylation regulates relative utilization of processing pathways for Alzheimer beta/A4 amyloid precursor protein.
abstract: The Alzheimer amyloid precursor protein (APP) is a phosphoprotein, and the phosphorylation state of APP at Ser655 can be regulated by protein kinase C, calcium/calmodulin-dependent protein kinase II, and okadaic acid-sensitive protein phosphatases. Other enzymes may also play a role at Ser655 of APP and, perhaps, at other residues. Signal transduction via protein phosphorylation regulates APP metabolism. In particular, APP processing via the nonamyloidogenic secretory cleavage pathway is increased following the activation of protein kinase C or the inactivation of okadaic acid-sensitive protein phosphatases. The mechanism(s) by which protein phosphorylation regulates APP secretory cleavage include (among others): substrate activation, substrate redistribution, protease activation and/or protease redistribution. Current experimental evidence will be discussed, addressing the relative importance of each of these possibilities and the implications for these events in the modulation of beta/A4-amyloidogenesis.
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, New York 10021.
authors.forename: S E
authors.initials: SE
authors.lastname: Gandy
authors.forename: G L
authors.initials: GL
authors.lastname: Caporaso
authors.forename: J D
authors.initials: JD
authors.lastname: Buxbaum
authors.forename: O
authors.initials: O
authors.lastname: de Cruz Silva
authors.forename: K
authors.initials: K
authors.lastname: Iverfeldt
authors.forename: C
authors.initials: C
authors.lastname: Nordstedt
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: A J
authors.initials: AJ
authors.lastname: Czernik
authors.forename: A C
authors.initials: AC
authors.lastname: Nairn
authors.forename: P
authors.initials: P
authors.lastname: Greengard
mesh_terms: D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000818:Animals; D006801:Humans; D016716:PC12 Cells; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012694:Serine
chemical_list: D016564:Amyloid beta-Protein Precursor; D010750:Phosphoproteins; D012694:Serine