Recruitment of casein kinase 2 is involved in AbetaPP processing following cholinergic stimulation

• Published in: Journal of Alzheimer's disease Vol. 20; no. 4; pp. 1133 - 1141
• Main Authors: Lenzken, Silvia C, Stanga, Serena, Lanni, Cristina, De Leonardis, Fabio, Govoni, Stefano, Racchi, Marco
• Format: Journal Article
• Language: English
• Published: Netherlands 2010
• Subjects: ADAM Proteins - metabolism; ADAM10 Protein; ADAM17 Protein; Amyloid beta-Protein Precursor - metabolism; Amyloid Precursor Protein Secretases - metabolism; Blotting, Western; Carbachol - pharmacology; Casein Kinase II - physiology; Cell Line; Cholinergic Agonists - pharmacology; Humans; Immunohistochemistry; Immunoprecipitation; Membrane Proteins - metabolism; Muscarinic Agonists - pharmacology; Parasympathetic Nervous System - metabolism; Protein Kinase C-epsilon - metabolism; Protein Processing, Post-Translational - drug effects; Tubulin - metabolism
• ISSN: 1875-8908
• DOI: 10.3233/JAD-2010-090232

The amyloid-beta protein precursor (AbetaPP) is an integral membrane protein subjected to constitutive and regulated proteolytic processing. We have previously demonstrated that protein kinase C epsilon (PKCepsilon) plays a key role in the regulation of AbetaPP metabolism via cholinergic receptors. The purpose of the present work is to clarify whether other putative signaling systems are involved in the same pharmacological pathway. We focused particularly on casein kinase 2 (CK2), demonstrating a direct interaction between PKCepsilon and CK2 following cholinergic stimulation. Treatment of human neuroblastoma SH-SY5Y cells with a selective inhibitor of CK2 reduced the effect of carbachol on the release of sAbetaPPalpha. This treatment did not influence the activation and translocation of PKCepsilon suggesting that the latter is located upstream of CK2. On the basis of our results, we add another player to the complex cellular mechanisms regulating non-amyloidogenic processing of AbetaPP.