title: Two-steps control of cellular prion physiology by the extracellular regulated kinase-1 (ERK1).
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.
authors.affiliation: Institut de Pharmacologie Moléculaire et Cellulaire and Institut de NeuroMédecine Moléculaire, Equipe labellisée Fondation pour la Recherche Médicale, Valbonne, France. checler@ipmc.cnrs.fr
authors.forename: Frédéric
authors.initials: F
authors.lastname: Checler
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D006801:Humans; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D008954:Models, Biological; D011328:Prions / Q000502:physiology*; D011499:Protein Processing, Post-Translational
chemical_list: D016564:Amyloid beta-Protein Precursor; D011328:Prions; D048052:Mitogen-Activated Protein Kinase 3; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human