title: Amyloid beta peptide directly inhibits PKC activation.
abstract: A putative protein kinase C (PKC) pseudosubstrate domain in beta amyloid (Abeta) suggests a potential interaction between Abeta and PKC. In this study, we investigated whether and how Abeta interacts with PKC. Abeta peptides inhibited PKC phosphorylation in a dose-dependent manner in cell-free in vitro condition, suggesting a direct interaction between Abeta and PKC. Experiments involving deletion of the Abeta sequence indicated that the putative PKC pseudosubstrate domain (Abeta 28-30) is critical for Abeta-PKC interaction. Addition of Abeta peptides to cultured B103 cells reduced the activated forms of PKCalpha and PKCepsilon. It also inhibited phorbol-12,13-dibutyrate (PDBu)-induced membrane translocation of PKCalpha and PKCepsilon without altering their expression levels, indicating that activation of intracellular PKC is inhibited by treatment of Abeta peptides. These results suggest that Abeta peptides inhibit PKC activation via direct interactions, which may play a role in pathogenesis of AD.
authors.affiliation: Department of Biology, College of Natural Sciences, Seoul National University, South Korea.
authors.forename: Woojin
authors.initials: W
authors.lastname: Lee
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Boo
authors.forename: Min Whan
authors.initials: MW
authors.lastname: Jung
authors.forename: Sang Dai
authors.initials: SD
authors.lastname: Park
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Seung U
authors.initials: SU
authors.lastname: Kim
authors.forename: Inhee
authors.initials: I
authors.lastname: Mook-Jung
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000503:physiopathology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D025461:Feedback, Physiological / Q000502:physiology; D009474:Neurons / Q000201:enzymology*; D010446:Peptide Fragments / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); D015240:Phorbol 12,13-Dibutyrate; C497257:Prkce protein, rat; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon