Affiliations: Department of Experimental and Applied Pharmacology, Centre of Excellence in Applied Biology, University of Pavia, Pavia, Italy
Correspondence:
[*]
Correspondence to: Marco Racchi, Dept. of Experimental and Applied Pharmacology, University of Pavia, Viale Taramelli 14, 27100 Pavia, Italy. Tel.: +39 0382 987738; Fax: +39 0382 987405; E-mail: racchi@unipv.it.
Note: [1] Present affiliation: Department of Biotechnology and Biosciences, University of Milano Bicocca, Milano, Italy.
Note: [2] Present affiliation: Department of Biochemistry “A. Castellani”, University of Pavia, Pavia, Italy.
Abstract: The amyloid-β protein precursor (AβPP) is an integral membrane protein subjected to constitutive and regulated proteolytic processing. We have previously demonstrated that protein kinase C ε (PKCε) plays a key role in the regulation of AβPP 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 PKCε 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 sAβPPα. This treatment did not influence the activation and translocation of PKCε 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 AβPP.
Keywords: Alzheimer's disease, amyloid-β protein precursor, casein kinase 2, cholingergic, neuroblastoma, protein kinase C, signal transduction
