Processing of Alzheimer's disease-associated beta-amyloid precursor protein.
Studies were undertaken on the processing of Alzheimer's disease-associated beta-amyloid precursor protein in normal cultured human fibroblasts and a human neuroblastoma cell line. Major differences in processing between the secreted and intracellular forms of the precursor were found. The intracellular form appears to undergo amino-terminal processing yielding many smaller fragments, whereas the secreted form does not show any further proteolytic cleavage after its release from the cell surface. In pulse-chase experiments, antibodies to the A4 region immunoprecipitated bands of Mr = 92,000-128,000, which represent the intact precursor; several smaller intracellular fragments of Mr = 70,000-72,000, 55,000, 33,000 and 6,000 also immunoprecipitated with this antibody. The Mr = 6,000 band cleared from the cell very quickly and is postulated to be the A4-carrying remnant of the secreted protein. The data show that a fragment of Mr = 33,000, which includes the A4 region, is one stable processed end-product of the intracellular precursor protein. It is possible that different posttranslational modifications are the signals responsible for the differences in processing between the secreted and intracellular amyloid precursor protein.
Dewji
N N
NN
Department of Medicine, School of Medicine, University of California, San Diego, La Jolla 94304.
Shelton
E R
ER
Adler
M J
MJ
Chan
H W
HW
Seegmiller
J E
JE
Coronel
C
C
D000544:Alzheimer Disease; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D009447:Neuroblastoma; D010446:Peptide Fragments / Q000032:analysis; D011498:Protein Precursors / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D014407:Tumor Cells, Cultured / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D011498:Protein Precursors