Protein kinase C-dependent alpha-secretory processing of the amyloid precursor protein is mediated by phosphorylation of myosin II-B.
A substantial body of evidence indicates that protein kinase C (PKC) is involved in the alpha-secretory processing of the amyloid precursor protein (APP), an event that reduces the formation of the pathogenic amyloid-beta peptide. Recently, we have shown that trafficking and processing of APP are both impaired by knockdown of myosin II-B, one of the major neuronal motor proteins. Here, we provide evidence that the alpha-secretory processing of APP is mediated by PKC-dependent phosphorylation of myosin II-B. This signaling pathway provides an important link between APP and the neuronal cytoskeleton and might be crucial for the understanding of the biological and pathological roles of APP.
Argellati
Francesca
F
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
Domenicotti
Cinzia
C
Passalacqua
Mario
M
Janda
Elzbieta
E
Melloni
Edon
E
Marinari
Umberto M
UM
Pronzato
Maria A
MA
Ricciarelli
Roberta
R
D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D006801:Humans; D007700:Kinetics; D051379:Mice; D009474:Neurons / Q000378:metabolism; D024501:Nonmuscle Myosin Type IIB / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D016564:Amyloid beta-Protein Precursor; D051571:Protein Kinase C-alpha; D024501:Nonmuscle Myosin Type IIB; D013755:Tetradecanoylphorbol Acetate