The anti-apoptotic molecules Bcl-xL and Bcl-w target protein phosphatase 1alpha to Bad

Bcl-xL and Bcl-W specifically interact with PP1alpha and Bad. A Phosphatase activity sensitive to okadaic acid was detected in Bcl-xL, Bcl-W and Bad immunoprecipitates. Serine phosphorylation of Bcl-xL and Bcl-W correlates with the number of trimolecular complexes formed. Depletion of Bcl-xL and Bcl-W decreases the remaining Bad-associated Phosphatase activity and association of protein Phosphatase 1 (PP1)alpha to Bad. Bcl-xL and Bcl-W contain the R/K X V/I X F consensus motif shared by PP1 targeting subunits. This motif, in addition to F X X R X R motif, is involved in binding of Bcl-xL and Bcl-W to PP1alpha. Disruption of Bcl-xL/PP1alpha or Bcl-W/PP1alpha association strongly decreases Bad-associated phosphataseactivity and stability of trimolecular complexes. These results suggest that Bcl-xL and Bcl-W are PP1alpha targeting subunits and this trimolecular complex may be involved in the control of Apoptosis.