FIG 8.
Fyn, SHP-1, and SHP-2 activities are regulated directly by H2O2 and a proposed scheme for DJ-1 regulation of ROS and downstream signals. (A and B) Activities of immunoprecipitated Fyn, SHP-1, and SHP-2 from non-stimulated (NS) and antigen-stimulated (Ag) BMMCs were assayed in vitro with different concentrations of H2O2 for 15 min. Values (means ± SEM) are from three independent experiments: * P < 0.05. (C) Representative confocal images and Western blot images for co-immunoprecipitation of LAT and SHP-1 or Syk and SHP-2. (D) Proposed scheme: Absence of DJ-1 leads to excess ROS which inhibits SHP-1 and enhances phosphorylation of LAT and LAT-dependent signals while inhibiting Fyn and, via activation of SHP-2, Syk. Nevertheless, the enhancement of LAT phosphorylation is sufficient to ultimately augment mediator release in DJ-1-deficient BMMCs and PCA in DJ-1-deficient mice.
