TY - JOUR
T1 - Secretory processing of the Alzheimer amyloid β A4 protein precursor is increased by protein phosphorylation
AU - Gillespie, Susan L.
AU - Golde, Todd E.
AU - Younkin, Steven G.
PY - 1992/9/30
Y1 - 1992/9/30
N2 - The 39-43 residue polypeptide (amyloid β protein, βA4) deposited as amyloid in Alzheimer's disease (AD) is derived from a set of 695-770 residue precursors referred to as the amyloid βA4 protein precursor (βAPP). In each of the 695, 751, and 770 residue precursors, the 43 residue βA4 is an internal peptide that begins 99 residues from the COOH-terminus of the βAPP. Each holoform is normally cleaved within the βA4 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 βA4 peptide. In this study, we employ cells stably transfected with full length βAPP695, βAPP751, or βAPP770 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 βAPP in the secretory pathway, PKC phosphorylation may help to prevent amyloid deposition.
AB - The 39-43 residue polypeptide (amyloid β protein, βA4) deposited as amyloid in Alzheimer's disease (AD) is derived from a set of 695-770 residue precursors referred to as the amyloid βA4 protein precursor (βAPP). In each of the 695, 751, and 770 residue precursors, the 43 residue βA4 is an internal peptide that begins 99 residues from the COOH-terminus of the βAPP. Each holoform is normally cleaved within the βA4 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 βA4 peptide. In this study, we employ cells stably transfected with full length βAPP695, βAPP751, or βAPP770 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 βAPP in the secretory pathway, PKC phosphorylation may help to prevent amyloid deposition.
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U2 - 10.1016/0006-291X(92)90442-N
DO - 10.1016/0006-291X(92)90442-N
M3 - Article
C2 - 1417805
AN - SCOPUS:0026662356
SN - 0006-291X
VL - 187
SP - 1285
EP - 1290
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -