title: A serine protease in Alzheimer's disease cells cleaves a 16K-peptide with flanking residues upstream to beta-amyloid-N-terminus as natural substrate.
abstract: A serine protease which cleaves an oligopeptide at the beta-amyloid (beta A4) N-terminus was identified and purified from extracellular fluid of familial Alzheimer's disease (FAD) lymphoblastoid cells. In order to search for a natural substrate that stands for a direct precursor of beta A4, C-terminal fragments of beta-amyloid precursor protein (APP) were prepared by immunoprecipitation of cytosol proteins with beta A4-specific antibody. The 16 kDa peptide with N-terminus 30 amino acids upstream from the beta A4-N-terminus, also existing in other hematopoietic cells, was proved to be a natural substrate for the protease in human lymphoid cells. Its cleaved fragment with beta A4-N-terminus was thought to be less amyloidogenic on the basis of its property of self-aggregation in acidic pH. The results suggest the significance of the unique cleavage site at beta A4-upstreams in generation and accumulation of beta A4.
authors.affiliation: Department of Radiation Biophysics and Genetics, Kobe University School of Medicine, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Matsumoto
authors.forename: R
authors.initials: R
authors.lastname: Matsumoto
authors.forename: H
authors.initials: H
authors.lastname: Baba
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiwara
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D015153:Blotting, Western; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D010455:Peptides / Q000378:metabolism; D011233:Precipitin Tests; D012697:Serine Endopeptidases / Q000378:metabolism*; D013379:Substrate Specificity / Q000502:physiology
chemical_list: D016229:Amyloid beta-Peptides; D010455:Peptides; D012697:Serine Endopeptidases