title: Regulated cleavage of Alzheimer beta-amyloid precursor protein in the absence of the cytoplasmic tail.
abstract: Alzheimer beta-amyloid precursor protein can be phosphorylated on residues Thr654, Ser655 and Thr668 on its cytoplasmic domain. Proteolytic cleavage of the amyloid precursor protein and release of the amyloid precursor protein ectodomain into the medium of cultured cells can be activated by phorbol esters which stimulate protein kinase C. In the present study, using mutated amyloid precursor protein, we show that phosphorylation of cytoplasmic residues is not required for the phorbol ester-activated cleavage and release of the amyloid precursor protein ectodomain. Remarkably, deletion of the entire amyloid precursor protein cytoplasmic tail had no effect on the phorbol ester-activated cleavage/release. The results indicate that activation of amyloid precursor protein cleavage/release by protein kinase C involves phosphorylation of some component of the processing pathway, instead of or in addition to the cytoplasmic tail of the amyloid precursor protein.
authors.affiliation: Rockefeller University, New York, NY 10021.
authors.forename: O A
authors.initials: OA
authors.lastname: da Cruz e Silva
authors.forename: K
authors.initials: K
authors.lastname: Iverfeldt
authors.forename: T
authors.initials: T
authors.lastname: Oltersdorf
authors.forename: S
authors.initials: S
authors.lastname: Sinha
authors.forename: I
authors.initials: I
authors.lastname: Lieberburg
authors.forename: T V
authors.initials: TV
authors.lastname: Ramabhadran
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: S S
authors.initials: SS
authors.lastname: Sisodia
authors.forename: S
authors.initials: S
authors.lastname: Gandy
authors.forename: P
authors.initials: P
authors.lastname: Greengard
mesh_terms: D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010766:Phosphorylation; D014162:Transfection
chemical_list: D016564:Amyloid beta-Protein Precursor; D015240:Phorbol 12,13-Dibutyrate