Clustering of cellular prion protein induces ERK1/2 and stathmin phosphorylation in GT1-7 neuronal cells.
The physiological role of the prion protein is largely unknown. Here, clustering of prion at the surface of GT1-7 cells was observed upon anti-prion antibody treatments. This clustering was associated with a rapid and transient phosphorylation of the mitogen activated protein kinases (MAPKs) extracellular receptor kinases 1 and 2 (ERK1/2), and also of the microtubule-destabilizing protein stathmin at serine 16. The specificity of this antibody-mediated activation was ascertained by its inhibition by prion small interfering RNA. The phosphorylation of ERK1/2 but not that of stathmin was abolished by the MAPK/ERK kinase 1 inhibitor U0126, whereas both signaling pathways were blocked by the specific inhibitor of the epidermal growth factor receptor AG1478, suggesting the likely recruitment of this receptor upon prion clustering.
Signalisation et Différenciation Cellulaires dans les Systèmes Nerveux et Musculaire, U440 INSERM/UPMC, Institut du Fer à Moulin, 17 rue du Fer à Moulin, 75005 Paris, France.
Céline
C
Monnet
Julie
J
Gavard
René-Marc
RM
Mège
André
A
Sobel
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015153:Blotting, Western; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019084:Fluorescent Antibody Technique, Indirect; D051379:Mice; D018613:Microscopy, Confocal; D008868:Microtubule Proteins / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D009570:Nitriles / Q000494:pharmacology; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D018621:PrPC Proteins / Q000502:physiology*; D011799:Quinazolines; D034741:RNA, Small Interfering / Q000037:antagonists & inhibitors; D050777:Stathmin; D020032:Tyrphostins / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D002070:Butadienes; D004791:Enzyme Inhibitors; D008868:Microtubule Proteins; D009570:Nitriles; D010750:Phosphoproteins; D018621:PrPC Proteins; D011799:Quinazolines; D034741:RNA, Small Interfering; D050777:Stathmin; C493994:Stmn1 protein, mouse; D020032:Tyrphostins; C113580:U 0126; C101044:RTKI cpd; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3