Inhibition of Platelet-Derived Growth Factor and Epidermal Growth Factor Receptor Signaling Events after Treatment of Cells with Specific Synthetic Inhibitors of Tyrosine Kinase Phosphorylation

摘要: The receptor kinase activity associated with the epidermal growth factor (EGF) and platelet-derived (PDGF) plays an important role in ligand-induced signaling events. effect of specific, synthetic chemical inhibitors PDGF- EGF-mediated tyrosine autophosphorylation on were examined NIH 3T3 cells overexpressing PDGF or EGF receptors. Specific inhibition ligand-dependent autophosphorylation, PI3K activation, mitogen-activated protein (MAPK) cyclin E-associated cell proliferation was measured after treatment these inhibitors. A inhibitor exhibited specific inhibitory properties when tested for PDGF-induced MAPK activity, entry into S phase activity. showed selective EGF-induced In both cases, compounds found to be effective as inducers arrest accumulation G1 cycle ligand treatment. However, at high concentrations, observed exhibit some nonspecific effects demonstrated by attenuation progression. This demonstrates that it is critical use lowest concentration such will alter response under investigation, have confidence conclusions derived from are valid. We conclude experimental parameters signify useful end points measure relative selectivity affect receptor-mediated signal transduction.