Journal article
PrP C -related signal transduction is influenced by copper, membrane integrity and the alpha cleavage site
CL Haigh, VA Lewis, LJ Vella, CL Masters, AF Hill, VA Lawson, SJ Collins
Cell Research | NATURE PUBLISHING GROUP | Published : 2009
DOI: 10.1038/cr.2009.86
Abstract
The copper-binding, membrane-anchored, cellular prion protein (PrP C) has two constitutive cleavage sites producing distinct N- and C-terminal fragments (N1/C1 and N2/C2). Using RK13 cells expressing either human PrP C, mouse PrP C or mouse PrP C carrying the 3F4 epitope, this study explored the influence of the PrP C primary sequence on endoproteolytic cleavage and one putative PrP C function, MAP kinase signal transduction, in response to exogenous copper with or without a perturbed membrane environment. PrP C primary sequence, especially that around the N1/C1 cleavage site, appeared to influence basal levels of proteolysis at this location and extracellular signal-regulated kinase 1/2 (ER..
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Awarded by NHMRC Program
Awarded by NH&MRC Career Development Award
Funding Acknowledgements
CF10 cells were a kind gift from Dr Suzette Priola (National Institutes of Health, USA). The authors thank Ms Robyn Sharples (The University of Melbourne, Australia) for technical assistance. This work was supported by an NH&MRC Program Grant (400202). CLH is supported by a University of Melbourne Early Career Researcher Grant; SJC by an NH&MRC Practitioner Fellowship (400183); SJC and VAL by an NH&MRC Project Grant (454546); VAL is supported by a University of Melbourne CR Roper Fellowship; VAL and AFH by an NH&MRC Project Grant (400229); and AFH by an NH&MRC Career Development Award (251745).