The mammalian Ras GTPase-activating protein (p120) interacts with activated members of the Ras superfamily of GTP-binding proteins to accelerate their deactivation by sharply increasing their rates of GTP hydrolysis. Among the Ras-family proteins interacting with p120 is Rap1A/Krev1, whose activity is not affected by p120 but which competes with Ras for p120. A second protein that interacts with p120 is p190, which activates the GTPase of guanine nucleotide-binding proteins of the Rho family (including Rac1 and Rac2). Both these p120-binding proteins are of interest in connection with the regulation of the respiratory burst oxidase, Rap1A/Krev1 because it copurifies with cytochrome b, and p190 because it inhibits the Rac2-dependent activation of the respiratory burst oxidase in a cell-free system. Using an 18-mer antisense oligonucleotide, we were able to decrease the expression of p120 in Epstein-Barr virus-transformed B lymphocytes. Under conditions where p120 expression was significantly depressed by antisense oligonucleotides, we observed a 40% increase in protein kinase C-dependent but not receptor-dependent O production. In contrast, sense and scrambled oligonucleotides had no effect on either p120 expression or O production. Our results suggest a role for p120 as a negative regulator in the protein kinase C-mediated activation of the respiratory burst oxidase.

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