Research Group of Prof. Dr. Helmut W. Klein
Institute of Biochemistry
Molecular Enzymology
Our focus of interest is the catalytic mechanism of receptor tyrosine kinases. One main subject of investigation is the the activation mechanism of Insulin Receptor (IR)- and Insulin-like Growth Factor Receptor (IGF-1R)-Kinases. We are interested in how dimerization does influence kinase activation, and we are looking for compounds that inhibit or trigger kinase dimerization. The second subject deals with the dual kinase activity of IR- and IGF-1R-Kinase. Under in vitro conditions, the dual kinase activity is without influence on the phosphoryl transfer activity regarding tyrosine kinase residues and the binding of SH2 domains. Under in vivo conditions, however, auto-serine phosphorylation and serine phosphorylation of the substrate (IRS1) resulting from dual kinase activity have a significant influence on the composition of signal transduction complexes, indicating the inhibition of SH2 domain interaction. Therefore, we look for proteins that cause the discrepancy between in vitro and in vivo conditions.
The Insulin Receptor Kinase Activation loop
