Identification and characterization of C-terminal fragments of the beta-amyloid precursor produced in cell culture.
The mechanism of amyloid formation in Alzheimer's disease is unknown but appears to involve proteolytic processing of the amyloidogenic peptide from a larger precursor. When the C-terminus containing the amyloid-forming and cytoplasmic domains of the precursor was recombinantly expressed in cultured mammalian cells, a 16 kd protein accumulated which had a tendency to aggregate and form deposits. These deposits had physical characteristics resembling those of preamyloid. Recombinant expression of the full-length precursor was found to produce a similar, cell-associated 16 kd C-terminal fragment as well as a 12 kd fragment, neither of which formed detectable aggregates suggesting efficient catabolism of these fragments. Identification of these two naturally occurring metabolic products of the beta-amyloid precursor provides a system permitting the characterization of the proteolytic processing events of the amyloid precursor protein.
Wolf
D
D
California Biotechnology Inc., Mountain View 94043.
Quon
D
D
Wang
Y
Y
Cordell
B
B
D000544:Alzheimer Disease / Q000378:metabolism; D000595:Amino Acid Sequence; D000682:Amyloid / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D016564:Amyloid beta-Protein Precursor; D000818:Animals; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes / Q000032:analysis; D005455:Fluorescent Antibody Technique; D006801:Humans; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000032:analysis / Q000276:immunology; D013194:Staining and Labeling; D014162:Transfection; D014616:Vaccinia virus / Q000235:genetics
D000682:Amyloid; D016564:Amyloid beta-Protein Precursor; D000939:Epitopes; D011498:Protein Precursors; D011994:Recombinant Proteins