PP1 and CGP76030 inhibition of Bcr-Abl.

PP1 and CGP76030 inhibit Bcr-Abl in a concentration-dependent manner to induce apoptosis in 32D_Bcr-Ablwt cells. (A-B) Structural formula of the kinase inhibitors CGP76030 and PP1. (C-D) Cos7 cells were transfected with either pApuro or Bcr-Ablwt. Cells were either left untreated or incubated with the indicated concentrations of CGP76030 and PP1 4 hours prior to lysis. Phosphorylation of Bcr-Abl and cellular proteins was assessed with the use of anti–phospho-Abl or antiphosphotyrosine antibodies. Expression of Bcr-Abl was controlled by means of anti-Abl antibody. (E-F) Survival (solid line) and proliferation (dashed line) of 32D_Bcr-Ablwt cells in the presence of the indicated concentrations of PP1 (panel E) or CGP76030 (panel F).