Figure 7.

Vav2 induces Nox1-dependent ROS generation through a Rac-dependent mechanism. (A) The increase in ROS formation caused by the presence of constitutively active Vav2 (Vav2-CA) is blocked in HEK293 cells by the cotransfection of dominant-negative Rac1 (RacN17) and/or is prevented by Nox1 TM unable to bind Rac. HEK293 cells were transfected with empty vector or with NoxO1 and NoxA1, and, where indicated, with SrcYF, Vav2-CA, RacN17, and Nox1 wt or Nox1 TM. The ROS production was checked after 24 h (top). All transfected proteins were expressed at similar levels (bottom). One representative experiment from three separate experiments is shown and results are given as mean of triplicates ± SD. (B) A schematic representation of the mechanism described in this paper through which c-Src induces the Nox1-dependent ROS generation in HT29 cells. c-Src activates the member of the Rac-GEF superfamily Vav2 by tyrosine-phosphorylation, thereby increasing the cellular levels of Rac1-GTP and leading to the generation of superoxide anion by Nox1.