Abstract
Cellular prion (PrP(c)) undergoes a regulated α-secretase-like cleavage by the disintegrin ADAM17 similar to the one taking place on β-amyloid precursor protein (βAPP). Because these cleavages give rise to biologically active fragments, understanding their regulation could be of importance. We have established that the Extracellular Regulated Kinase-1 (ERK1) controls PrPc processing by modulating ADAM17 phosphorylation in a protein kinase C-dependent manner. Strikingly, we also demonstrated that ERK1 acts upstream to increase PrP(c) promoter transactivation in an AP-1 dependent manner. Therefore, ERK1 exerts a dual control of both PrP(c) metabolism and expression. Interestingly, α-secretase cleavage of βAPP appears to be independent of ERK1. I describe here similarities and differences in α-secretase-mediated PrP(c) and βAPP processing pathways and discuss putative physiopathological implications.