title: Regulation of amyloid precursor protein release by protein kinase C in Swiss 3T3 fibroblasts.
abstract: Release of the amyloid precursor protein (APP) of Alzheimer's disease from Swiss 3T3 fibroblasts was stimulated in a concentration-dependent manner by phorbol 12-myristate 13-acetate. In fibroblasts overexpressing protein kinase C alpha (PKC alpha), the EC50 for this response was 7 nM, while in control cells the EC50 was 63 nM. The effect of PMA was inhibited by the PKC antagonist H-7 in control cells, but not in cells that overexpressed PKC alpha. Basal release of APP was higher in cells that overexpressed PKC alpha, and was not affected by the phosphatase inhibitor okadaic acid, although this compound doubled APP release from control cells. The results suggest that PKC alpha regulates APP processing in mammalian cells. Alterations in the activity of PKC have been reported to occur in Alzheimer's disease and might potentially contribute to abnormalities of APP metabolism characteristic of this disorder.
authors.affiliation: Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
authors.forename: B E
authors.initials: BE
authors.lastname: Slack
authors.forename: R M
authors.initials: RM
authors.lastname: Nitsch
authors.forename: E
authors.initials: E
authors.lastname: Livneh
authors.forename: G M
authors.initials: GM
authors.lastname: Kunz
authors.forename: H
authors.initials: H
authors.lastname: Eldar
authors.forename: R J
authors.initials: RJ
authors.lastname: Wurtman
mesh_terms: D016475:3T3 Cells; D000544:Alzheimer Disease / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis*; D000818:Animals; D006801:Humans; D007700:Kinetics; D051379:Mice; D010766:Phosphorylation; D011493:Protein Kinase C / Q000096:biosynthesis / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
chemical_list: D016564:Amyloid beta-Protein Precursor; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate