Sustained Activation of Glial Cell Epidermal Growth Factor Receptor by Bis(thiosemicarbazonato) Metal Complexes Is Associated with Inhibition of Protein Tyrosine Phosphatase Activity
Katherine Ann Price, Aphrodite Caragounis, Brett M Paterson, Gulay Filiz, Irene Volitakis, Colin L Masters, Kevin J Barnham, Paul S Donnelly, Peter J Crouch, Anthony R White
JOURNAL OF MEDICINAL CHEMISTRY | AMER CHEMICAL SOC | Published : 2009
Bis(thiosemicarbazonato) metal complexes (M(II)(btsc)) have demonstrated potential neuroprotective activity in cell and animal models of Alzheimer's disease (AD). Metal complexes can activate the epidermal growth factor receptor (EGFR), leading to inhibition of amyloid peptide accumulation in neuronal cells. As glial cells also have an important role in modulating neuronal health and survival in AD, we examined the effect of M(II)(btsc) on activity of EGFR in an astroglial cell line. Our findings reveal potent activation of glial EGFR by glyoxalbis(N(4)-methylthiosemicarbazonato)Cu(II)] (Cu(II)(gtsm)). Activation of EGFR by Cu(II)(gtsm) involved phosphorylation of multiple tyrosine residues ..View full abstract
This work was supported by funding from the ANZ Charitable Trusts (J. O. & J. R. Wicking Trust), National Health and Medical Research Council of Australia, and Australian Research Council. K.J.B. is ail NHMRC Senior Research Fellow.