NR AOSD
AU Epple,G.; Kettelgerdes,G.; Schleuning,W.D.; Koettgen,E.; Gessner,R.; Praus,M.
TI Stimulation of Plasminogen Activation by Recombinant Prion Protein is Specific for Tissue-type Plasminogen Activator
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - BR-50
PT Konferenz-Poster
AB We have recently shown that the NH2-terminal fragment (23-110) of the human cellular prion protein (PrPc) stimulates t-PA mediated plasminogen activation and that the interaction of the prion protein with t-PA is mediated by the aminoterminal lysine cluster (K23, K24, K27). In this study we examined the stimulatory activity of recombinant PrP23-231 and PrP23-110 on plasminogen activation catalyzed by t-PA, u-PA, streptokinase and DSPAalpha1. We found that recombinant full-length prion protein, PrP23-231, and the fragment PrP23-110 specifically stimulate t- PA mediated plasminogen activation. It has been shown that the binding of PrPc to t-PA and other kringle-bearing proteins is mediated by the flexible NH2-terminal region of PrPc. We determined binding of the four different plasminogen activators to PrP23-110 using surface plasmon resonance technology. Our data show no specific binding for streptokinase. In contrast, all plasminogen activators carrying a kringle domain bound to PrP23-110. But only t-PA, which harbours a kringle domain with lysine binding sites, is significantly stimulated by the prion protein. The specific stimulation of t-PA mediated plasminogen activation by PrP suggests a biological function of PrP as a cofactor in the regulation of plasmin activity in the central nervous system.
AD G. Epple, G. Kettelgerdes, E. Koettgen, R. Gessner, M. Praus, Institut für Laboratoriumsmedizin, Charite Berlin, Germany; W.D. Schleuning, Schering Research Laboratories, Berlin, Germany; W.D. Schleuning, Paion GmbH, Forschungszentrum Berlin, Berlin, Germany
SP englisch
PO Deutschland