Cell Redox Redux

PI-3K Activation Leads to Reactive Oxygen Species Formation

Science's STKE  18 Apr 2000:
Vol. 2000, Issue 28, pp. tw7
DOI: 10.1126/stke.2000.28.tw7

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]