NR ATPF
AU Gyllberg,H.; Löfgren,K.M.; Bedecs,K.
TI Elevated Src kinase activity results in increased protein tyrosine phosphorylation in scrapie-infected neuronal cell lines
QU International Conference - Prion 2005: Between fundamentals and society's needs - 19.10.-21.10.2005, Congress Center Düsseldorf - Poster Session: Pathogenesis PATH-16
PT Konferenz-Poster
AB
Because both PrPc and PrPsc as well as Src-family kinases are localized to lipid rafts we have studied how the formation and accumulation of PrPsc in rafts may affect the Src kinase activity in two different scrapie-infected neuronal cell lines: ScGT1 and ScN2a, compared to their non-infected counter parts. By immunoblotting, using clone 28 - a monoclonal antibody specific for the active form of Src and Fyn kinases, we have found increased levels of both active Src and Fyn in ScGT1 and ScN2a cells. In vitro kinase assay confirmed the increased Src activity. Comparing the amount of active Src and Fyn to the amount of Src and Fyn protein levels, revealed an increased specific activity of Fyn, whereas the increased Src kinase activity was correlated to an elevated Src protein level.
In addition, an important increase in protein tyrosine phosphorylation was observed in ScGT1 and ScN2a cells, which was further shown to be Src-dependent, as treatment with PP2- a Src family kinase specific inhibitor, completely reversed the protein tyrosine phosphorylation profile.
Although several studies have shown that PrPc may interact with and/or activate Src family kinases, our study shows for the first time that abberantly expressed and regulated Src kinase activity result in increased protein Tyr phosphorylation in scrapie-infected neuronal cells. Abnormal Src-kinase activation and subsequent protein tyrosine phosphorylation may be key elements in the neuropathology of the prion diseases.
AD Hanna Gyllberg, Kajsa Löfgren, Katarina Bedecs, Stockholm University, Sweden
SP englisch
PO Deutschland