Abstract
Studies were undertaken on the processing of Alzheimer's disease-associated β-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 from 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-carring 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.
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This work was supported by grants from the National Institutes of Health (NS27580-01) and American Federation of Aging Research to N. Dewji, and grants PHS AR16322 and AG00402 to J.E. Seegmiller. M. Adler is a recipient of a Physician-Scientist Fellowship grant AG00353 to J.E. Seegmiller. The work was also supported by generous donations from the Patrons of Research of the Institute for Research on Aging, Mrs. Roberta Seegmiller, the Paul Glenn Foundation, and the Greenwall Foundation.
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Dewji, N.N., Shelton, E.R., Adler, M.J. et al. Processing of Alzheimer's disease-associated β-amyloid precursor protein. J Mol Neurosci 2, 19–27 (1990). https://doi.org/10.1007/BF02896922
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DOI: https://doi.org/10.1007/BF02896922