Prion protein induced signaling cascades in monocytes
- Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Muenchen (Germany)
- CNS Research III, Boehringer Ingelheim Pharma GmbH and Co KG, Biberach/Riss (Germany)
- Center for Neuropathology and Prion Research, Ludwig-Maximilians-University Munich, Munich (Germany)
- Department of Physiology and Biochemistry, University of Malta, Msida (Malta)
Prion proteins play a central role in transmission and pathogenesis of transmissible spongiform encephalopathies. The cellular prion protein (PrP{sup 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{sup C} fusion proteins synthesized with a human Fc-tag. PrP{sup 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{sub 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{sup C} in monocytes and macrophages.
- OSTI ID:
- 20798772
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 340, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2005.11.158; PII: S0006-291X(05)02707-5; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
Similar Records
Differential Accumulation of Misfolded Prion Strains in Natural Hosts of Prion Diseases
Activation by prion peptide PrP106–126 induces a NF-κB-driven proinflammatory response in human monocyte-derived dendritic cells