Amyloid beta peptide directly inhibits PKC activation.
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.
Lee
Woojin
W
Department of Biology, College of Natural Sciences, Seoul National University, South Korea.
Boo
Jung Hyun
JH
Jung
Min Whan
MW
Park
Sang Dai
SD
Kim
Young Ho
YH
Kim
Seung U
SU
Mook-Jung
Inhee
I
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
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