Abstract
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.
References
Jan 1, 1988·Journal of Medicinal Chemistry·J J NestorB H Vickery
Apr 7, 1989·Cell·A WeidemannK Beyreuther
Aug 26, 1988·Science·J S O'BrienA L Fluharty
Feb 19, 1987·Nature·J KangB Müller-Hill
Feb 11, 1988·Nature·P PonteF Fuller
Feb 11, 1988·Nature·R E TanziR L Neve
Feb 11, 1988·Nature·N KitaguchiH Ito
Feb 20, 1987·Science·R E TanziR L Neve
Jan 1, 1986·Annual Review of Biochemistry·D R Lynch, S H Snyder
Oct 11, 1988·Nucleic Acids Research·S MitaE A Schon
Oct 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·D J SelkoeT Oltersdorf
Jun 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·C L MastersK Beyreuther
Feb 20, 1987·Science·D GoldgaberD C Gajdusek
Jul 1, 1974·European Journal of Biochemistry·W M Bonner, R A Laskey
Aug 15, 1970·Nature·U K Laemmli
Dec 1, 1984·DNA·J R de WetD R Helinski
Jun 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·R A LernerT M Shinnick
May 16, 1984·Biochemical and Biophysical Research Communications·G G Glenner, C W Wong
Aug 1, 1981·Annals of Neurology·R D TerryD S Horoupian
Mar 1, 1980·Analytical Biochemistry·M BittnerC F Morris
Citations
Dec 31, 1992·Annals of the New York Academy of Sciences·R A NixonL Kanaley-Andrews
Jan 1, 1991·Comparative Biochemistry and Physiology. A, Comparative Physiology·X H ZhaoL K Duffy
Apr 1, 1994·The Journal of Comparative Neurology·J G BeesonF H Gage