title: Prion protein induced signaling cascades in monocytes.
abstract: Prion proteins play a central role in transmission and pathogenesis of transmissible spongiform encephalopathies. The cellular prion protein (PrP(C)), whose physiological function remains elusive, is anchored to the surface of a variety of cell types including neurons and cells of the lymphoreticular system. In this study, we investigated the response of a mouse monocyte/macrophage cell line to exposure with PrP(C) fusion proteins synthesized with a human Fc-tag. PrP(C) fusion proteins showed an attachment to the surface of monocyte/macrophages in nanomolar concentrations. This was accompanied by an increase of cellular tyrosine phosphorylation as a result of activated signaling pathways. Detailed investigations exhibited activation of downstream pathways through a stimulation with PrP fusion proteins, which include phosphorylation of ERK(1,2) and Akt kinase. Macrophages opsonize and present antigenic structures, contact lymphocytes, and deliver cytokines. The findings reported here may become the basis of understanding the molecular function of PrP(C) in monocytes and macrophages.
authors.affiliation: Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, München, Germany.
authors.forename: Bjarne
authors.initials: B
authors.lastname: Krebs
authors.forename: Cornelia
authors.initials: C
authors.lastname: Dorner-Ciossek
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Schmalzbauer
authors.forename: Neville
authors.initials: N
authors.lastname: Vassallo
authors.forename: Jochen
authors.initials: J
authors.lastname: Herms
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
mesh_terms: D000818:Animals; D002460:Cell Line; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011328:Prions / Q000378:metabolism* / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D011328:Prions; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt