NADPH oxidase and extracellular regulated kinases 1/2 are targets of prion protein signaling in neuronal and nonneuronal cells.
Putative functions of the cellular prion protein, PrPC, include resistance to oxidative stress, copper uptake, cell adhesion, and cell signaling. Here, we report NADPH oxidase-dependent reactive oxygen species (ROS) production and extracellular regulated kinases 1/2 (ERK1/2) phosphorylation on PrPC stimulation in the 1C11 neuroectodermal precursor, in its neuronal differentiated progenies, and in GT1-7 neurohypothalamic and BW5147 lymphoid cells. In neuroprogenitor, hypothalamic, and lymphoid cells, ERK1/2 activation is fully controlled by the NADPH oxidase-dependent ROS production. In 1C11-derived bioaminergic cells, ROS signaling and ERK1/2 phosphorylation are both controlled by Fyn kinase activation, introducing some specificity in PrPC transduction associated with this neuronal context. These data argue for an ubiquitous function of PrPC in cell-redox homeostasis through ROS production.
Schneider
Benoît
B
Différenciation Cellulaire et Prions, Centre National de la Recherche Scientifique Unité Propre de Recherche 1983, Institut André Lwoff, 7 Rue Guy Môquet, BP8, 94 801 Villejuif Cedex, France.
Mutel
Vincent
V
Pietri
Mathéa
M
Ermonval
Myriam
M
Mouillet-Richard
Sophie
S
Kellermann
Odile
O
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007031:Hypothalamus / Q000378:metabolism; D051379:Mice; D008856:Microscopy, Fluorescence; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D019255:NADPH Oxidases / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000378:metabolism*; D010084:Oxidation-Reduction; D010641:Phenotype; D010766:Phosphorylation; D011233:Precipitin Tests; D011328:Prions / Q000378:metabolism*; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D013997:Time Factors
D011328:Prions; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases