The comparison of the unnatural amino acid napthylalanine NfsB mutant and wild type NfsB activity for the pro-drug CB1954 and menadione; investigating the effect of the poly histidine tag on wild type NfsB substrate reduction; and G protein coupled cytokines fMLP & LPA induced potentiation of PDGF receptor signaling; protein kinase C: a possible point of signal integration for PDGF \(\beta\) receptor recycling.

[摘要] The first project investigated the enzyme NfsB from Eschericia coli (a bacterial Nitroreductase), which has now entered the clinical trial stage with the pro-drug [5-(aziridin-1-yl)-2,4-dinitrobenzamide] (CB1954). The activity of napthylalanine NfsB mutant with the CB1954 pro-drug was compared to that of the wild type NfsB. Furthermore the activity of wild type NfsB and the unnatural amino acid mutant napthylalanine with menadione were also determined. This study concluded that menadione is a better substrate for both the wild type and napthylalanine NfsB mutant, improving the specificity constant by 40/50 times. The napthylalanine NfsB mutant showed a statistically significant lower activity with the pro-drug in comparison to the wild type NfsB. The second project investigated the Platelet derived growth factor receptor PDGF \(\beta\), which investigated the current hypothesis that Protein Kinase C (PKC) is a point of signal integration for PDGF \(\beta\) receptor recycling. In this study the G protein coupled cytokines fMLP and a LPA were investigated. fMLP was an un-investigated cytokine, where this study showed it to potentiate and stimulate PDGF \(\beta\) receptor phosphorylation as well asinduce activation of PKC.This is early data supporting the hypothesis that PKC is a point of signal integration for PDGF \(\beta\) receptor recycling and that all signals which result in \(\beta\) receptor recycling must activate PKC.

[发布机构] University:University of Birmingham;Department:School of Biosciences

[关键词] Q Science;QH Natural history;QH301 Biology