Figure 6: c-Cbl down-regulates the MLK3-ASK1-p38MAPK stress pathway leading to apoptosis. The c-Cbl associated p38 expression appears not to depend on the molecular adaptor Grb-2. A) Overview of p38MAPK stress signalling pathway summarized from Matsuzawa and Ichijo [33] B to E) the expression of the kinases MLK3, ASK1, p38MAPK and phospho-p38MAPK have been compared in LNCaP cell line between control cells (siRNA control, column 1) and cells subjected to c-Cbl RNA interference (column 2). F): expression of p38MAPK in LNCaP cell line treated 6 hours by 25 μM hydrogen peroxide (H2O2) or untreated (NT), as indicated. Column 1: siRNA control cells, column 2: c-Cbl siRNA cells, column 3: Grb-2 siRNA cells, column 4: c-Cbl and Grb-2 siRNA cells. G): effects of c-Cbl RNA interference (#2), Grb-2 RNA interference (#3) and c-Cbl plus Grb-2 RNA interference (#4) compared to control (siRNA control, #1), respectively on c-Cbl and Grb-2 expressions in LNCaP cell line.