Oxidative Stress and Growth Factor-Mediated Signal Transduction

Reversible enzymatic phosphorylation of protein tyrosine residues is considered to be an important mechanism of cellular regulation. Such processes have been associated with the control of cellular proliferation, differentiation and transformation. Enhanced protein tyrosine phosphorylation is essential to the stimulation of cell proliferation by peptide growth factors. Growth factors bind to their specific receptors which contain protein tyrosine kinase activity and initiate a cascade of events which include receptor autophosphorylation on tyrosine residues and tyrosine phosphorylation of other proteins of the signal transduction pathway. Dephosphorylation of tyrosine residues on tyrosine phosphorylated proteins occurs by the action of protein tyrosine phosphatases. Oxidative stress may also play a role in growth factor-mediated signal transduction as evidenced by its effect on cellular growth. We have recently demonstrated that diamide or ascorbic acid has inhibitory effects on protein tyrosine phosphatases in intact murine fibroblasts transfected with the human EGF-receptor. This inhibition can be prevented by EGF, which implies that an interactional link exists between protein tyrosine phosphatase and protein tyrosine kinase activities in the signal transduction pathway of cell growth induced by EGF when cells are exposed to redox agents.