Oxidants in receptor tyrosine kinase signal transduction pathways

The accumulation of oxygen in the atmosphere created an evolutionary stress for organisms to survive because oxygen, while the by-product of photosynthesis and an important substrate in oxidative metabolism, can also be partially reduced to form toxic products. These forms of oxygen, reduced by one electron or two electrons, yield superoxide anion (O-2(,-)) and hydrogen peroxide (H2O2), respectively. Recent studies suggest that reactive oxygen species (ROS) such as O-2(.-) and H2O2 function as mitogenic mediators of activated growth-factor receptor signaling. Reported data imply that growth factor-stimulated ROS generation can mediate intracellular signaling pathways by activating protein tyrosine kinases, inhibiting protein tyrosine phosphatase, and regulating redox-sensitive gene expression. This review examines the mechanisms of growth factor-induced generation of ROS and their roles in specific receptor tyrosine kinase signaling pathways.