title: Amyloid precursor protein secretion and beta A4 amyloid generation are not mutually exclusive.
abstract: The cellular factors regulating the generation of beta A4 from the amyloid precursor protein (APP) are unknown. Protein phosphorylation by protein kinase C (PKC) has been found to influence the processing and metabolism of APP. In this report, we show that in the human neuroblastoma cell line SY5Y, beta A4 generation from full-length APP is not changed by PKC activation whereas production of the non-amyloidogenic secretory fragment (APPsec) and of the C-terminal fragment of beta A4 (p3) are stimulated. In addition, beta A4 generation from the membrane inserted C-terminal 100 residues (SPA4CT) of APP is stimulated by PKC activation. Accordingly attempts to divert APP processing from the amyloidogenic, beta A4-generating, to the non-amyloidogenic, secretory, pathway, have to address the nature and regulation of the two pathways and/or of the process leading to the cleavage of APP at the C-terminus of the beta A4 domain. The data reported here suggest that these mechanisms are cell-type specific.
authors.affiliation: Research Laboratories of Schering AG, Berlin, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Dyrks
authors.forename: U
authors.initials: U
authors.lastname: Mönning
authors.forename: K
authors.initials: K
authors.lastname: Beyreuther
authors.forename: J
authors.initials: J
authors.lastname: Turner
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D006801:Humans; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002217:Carbachol; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate