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

Abstract

Bcl-xL and Bcl-w specifically interact with PP1α 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)α 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 PP1α. Disruption of Bcl-xL/PP1α or Bcl-w/PP1α association strongly decreases Bad-associated phosphataseactivity and stability of trimolecular complexes. These results suggest that Bcl-xL and Bcl-w are PP1α targeting subunits and this trimolecular complex may be involved in the control of apoptosis.