Activation of several growth factor receptors leads to the production of H2O2 in cells. To identify what signal pathways are involved in eliciting H2O2 production, Bae et al. studied platelet-derived growth factor receptors (PDGFRs) that were deficient in activating specific intracellular signaling pathways. Only the PDGFR mutant that could not activate phosphatidylinositol-3' kinase (PI-3K) was unable to elicit H2O2 production. Also the intrinsic kinase activity of the PDGFR was demonstrated to be essential for H2O2 production. Expression of a membrane-targeted form of the PI-3K catalytic subunit (p110-CAAX) led to H2O2 production, indicating that plasma membrane recruitment may contribute to PI-3K-dependent H2O2 formation. H2O2 production was also dependent on the small guanosine triphosphatase (GTPase) Rac, as expression of a dominant negative Rac mutant blocked the PI-3K signal that activates, presumably, NADPH oxidase, the generator of cellular H2O2.
Bae, Y.S., Sung, J.-Y., Kim, O.-S., Kim, Y.J., Hur, K.C., Kazlauskas, A., and Rhee, S.G. (2000) Platelet-derived growth factor-induced H2O2 production requires the activation of phosphatidylinositol 3-kinase. J. Biol. Chem. 275: 10527-10531. [Abstract] [Full Text]
