An essential role for free radicals and derived species in signal transduction

It is well accepted that extracellular ligands trigger nuclear signals through a cascade of protein-protein interactions. Many of these pathways have been carefully defined and provide an important framework by which we can understand and intervene in the processes they initiate. Recent data in the literature indicate that many extracellular ligands generate and/or require reactive free radicals or derived species to successfully transmit their signals to the nucleus. Thus, a novel signaling mechanism akin to one solely dependent on protein-protein interactions may exist. Here, we review this information, identify both the sources and targets of free radicals generated by various growth factors and cytokines, discuss how specificity can be achieved, and explore the pathophysiological implications.