Amyloid beta peptide directly inhibits PKC activation

Abstract

A putative protein kinase C (PKC) pseudosubstrate domain in beta amyloid (Aβ) suggests a potential interaction between Aβ and PKC. In this study, we investigated whether and how Aβ interacts with PKC. Aβ peptides inhibited PKC phosphorylation in a dose-dependent manner in cell-free in vitro condition, suggesting a direct interaction between Aβ and PKC. Experiments involving deletion of the Aβ sequence indicated that the putative PKC pseudosubstrate domain (Aβ 28–30) is critical for Aβ–PKC interaction. Addition of Aβ peptides to cultured B103 cells reduced the activated forms of PKCα and PKCε. It also inhibited phorbol-12,13-dibutyrate (PDBu)-induced membrane translocation of PKCα and PKCε without altering their expression levels, indicating that activation of intracellular PKC is inhibited by treatment of Aβ peptides. These results suggest that Aβ peptides inhibit PKC activation via direct interactions, which may play a role in pathogenesis of AD.