Figure 6. Effect of MET inhibitor ARQ 197 on kinase activation profile and downstream signaling pathways in MPM.

The protein tyrosine kinase activity profile obtained using H513 lysates treated with ARQ 197 as tested on PamChip microarrays. The color-coded response signature (A) is shown as heatmap in which treatment related upregulation of kinase activity is shown by red and downregulation by blue. Protein tyrosine kinase activity is down regulated in a dose dependent manner for most of the peptides. (B) H2596 and H513 cells were starved in 0.5% BSA media for 16 to 18 h and then treated with ARQ 197 at indicated concentrations for 24 h. The cells were then stimulated with human recombinant HGF (100 ng/ml) for 15 min before preparing the cell lysates. Immunobloting was then performed with the following antibodies Phospho-MET^Y1234/1235, Phospho-MET^Y1003, Phospho-MET^Y1349, Phospho-Paxillin, Phospho-AKT ^Ser473, Phospho -AKT ^thr308, Phospho-ERK, phospho-S6K and the corresponding total antibodies.