Secretory processing of the Alzheimer amyloid beta/A4 protein precursor is increased by protein phosphorylation

Gillespie, S.L.; Golde, T.E.; Younkin, S.G.

Biochemical and Biophysical Research Communications 187(3): 1285-1290


ISSN/ISBN: 0006-291X
PMID: 1417805
Document Number: 394263
The 39-43 residue polypeptide (amyloid beta protein, beta-A4) deposited as amyloid in Alzheimer's disease (AD) is derived from a set of 695-770 residue precursors referred to as the amyloid beta-A4 protein precursor (beta-APP). In each of the 695, 751, and 770 residue precursors, the 43 residue beta-A4 is an internal peptide that begins 99 residues from the COOH-terminus of the beta-APP. Each holoform is normally cleaved within the beta-A4 to produce a large secreted derivative as well as a small membrane associated fragment. Neither of these derivatives can produce amyloid because neither contains the entire beta-A4 peptide. In this study, we employ cells stably transfected with full length beta-APP-695, beta-APP-751, or beta-APP-770 expression constructs to show that phorbol ester activation of protein kinase C substantially increases the production of secreted forms from each isoform. By increasing processing of beta-APP in the secretory pathway, PKC phosphorylation may help to prevent amyloid deposition.

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