Ras, superoxide and signal transduction.

The superoxide anion has been associated with the bactericidal activity of phagocytes. Produced by an enzymatic complex, NADPH oxidase, bactericidal superoxide is released within phagolysosomes where bacteria are being degraded. The activity of NADPH oxidase is regulated by Rac, a small GTP binding protein of the Ras family. Recent evidence indicates that, in addition to its bactericidal activity, superoxide seems to function as a signal-transduction messenger, mediating the downstream effects of Ras and Rac in nonphagocytic cells. As such, superoxide contributes to the unchecked proliferation of Ras-transformed cells. In the nitric oxide (NO) system, low concentrations of NO transduce signals within vessels and neurons, while high concentrations of NO can produce damage to cells and microorganisms. By analogy, superoxide and probably other oxidants serve as messengers at low concentrations, while larger amounts are required for inducing damage. The activity of oxidants as messengers opens new avenues for pharmacological intervention against Ras-mediated pathways in mammalian cells.