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

Eur J Immunol. 2002 Jul;32(7):1847-55. doi: 10.1002/1521-4141(200207)32:7<1847::AID-IMMU1847>3.0.CO;2-7.


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.

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins
  • Apoptosis*
  • Binding Sites
  • Carrier Proteins / metabolism*
  • Cell Line
  • Enzyme Inhibitors / pharmacology
  • HeLa Cells
  • Humans
  • Mice
  • Okadaic Acid / pharmacology
  • Phosphoprotein Phosphatases / antagonists & inhibitors
  • Phosphoprotein Phosphatases / metabolism*
  • Protein Phosphatase 1
  • Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • bcl-Associated Death Protein
  • bcl-X Protein


  • Apoptosis Regulatory Proteins
  • BAD protein, human
  • BCL2L1 protein, human
  • BCL2L2 protein, human
  • Bad protein, mouse
  • Bcl2l1 protein, mouse
  • Bcl2l2 protein, mouse
  • Carrier Proteins
  • Enzyme Inhibitors
  • Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-Associated Death Protein
  • bcl-X Protein
  • Okadaic Acid
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1