Specific Cleavage of β-Amyloid Precursor Protein by an Integral Membrane Metalloendopeptidase
The β-amyloid precursor protein (ß-APP) is a membrane spanning glycoprotein. The small ß-protein domain within the precursor is presumed to be the source of amyloid found in plaques characteristic of Alzheimer’s Disease. The amino terminus of ß-APP is released from cells by cleavages that produce both potentially amyloidogenic and non-amyloidogenic fragments of the carboxy terminus (Esch et al., 1990; Anderson et al., 1992; Seubert et al., 1993; Golde et al., 1992; Haas et al., 1992; Sisodia, 1992). Attenuating these cleavages could alter the amount of ß-protein produced by cells. To facilitate understanding the cellular processes that control ß-protein production, we have developed a system to identify the proteolytic enzymes involved. The system was used to characterize a cellular activity that cleaves at Lys16 within the ß-protein.
KeywordsMembrane Fraction Cell Free System Specific Cleavage Mercaptoacetic Acid Alzheimer Amyloid Protein Precursor
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