Recruitment of casein kinase 2 is involved in AbetaPP processing following cholinergic stimulation.
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.
Lenzken
Silvia C
SC
Department of Experimental and Applied Pharmacology, Centre of Excellence in Applied Biology, University of Pavia, Pavia, Italy.
Stanga
Serena
S
Lanni
Cristina
C
De Leonardis
Fabio
F
Govoni
Stefano
S
Racchi
Marco
M
D051722:ADAM Proteins / Q000378:metabolism; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D015153:Blotting, Western; D002217:Carbachol / Q000494:pharmacology; D047390:Casein Kinase II / Q000502:physiology*; D002460:Cell Line; D018679:Cholinergic Agonists / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000378:metabolism; D018721:Muscarinic Agonists / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D014404:Tubulin / Q000378:metabolism
D016564:Amyloid beta-Protein Precursor; D018679:Cholinergic Agonists; D008565:Membrane Proteins; D018721:Muscarinic Agonists; D014404:Tubulin; D002217:Carbachol; D047390:Casein Kinase II; D051744:Protein Kinase C-epsilon; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; D000072198:ADAM17 Protein