BAD Ser-155 phosphorylation regulates BAD/Bcl-XL interaction and cell survival

J Biol Chem. 2000 Aug 18;275(33):25865-9. doi: 10.1074/jbc.M004199200.


The BH3 domain of BAD mediates its death-promoting activities via heterodimerization to the Bcl-XL family of death regulators. Growth and survival factors inhibit the death-promoting activity of BAD by stimulating phosphorylation at multiple sites including Ser-112 and Ser-136. Phosphorylation at these sites promotes binding of BAD to 14-3-3 proteins, sequestering BAD away from the mitochondrial membrane where it dimerizes with Bcl-XL to exert its killing effects. We report here that the phosphorylation of BAD at Ser-155 within the BH3 domain is a second phosphorylation-dependent mechanism that inhibits the death-promoting activity of BAD. Protein kinase A, RSK1, and survival factor signaling stimulate phosphorylation of BAD at Ser-155, blocking the binding of BAD to Bcl-XL. RSK1 phosphorylates BAD at both Ser-112 and Ser-155 and rescues BAD-mediated cell death in a manner dependent upon phosphorylation at both sites.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 14-3-3 Proteins
  • Amino Acid Sequence
  • Carrier Proteins / chemistry*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Line
  • Cell Survival
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Cytoplasm / metabolism
  • DNA, Complementary / metabolism
  • Glutathione Transferase / metabolism
  • Humans
  • Immunoblotting
  • Mitochondria / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Phosphorylation
  • Plasmids / metabolism
  • Precipitin Tests
  • Protein Structure, Tertiary
  • Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / chemistry*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Ribosomal Protein S6 Kinases, 90-kDa*
  • Serine / metabolism*
  • Tyrosine 3-Monooxygenase*
  • bcl-Associated Death Protein
  • bcl-X Protein


  • 14-3-3 Proteins
  • BAD protein, human
  • BCL2L1 protein, human
  • Carrier Proteins
  • DNA, Complementary
  • Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins
  • bcl-Associated Death Protein
  • bcl-X Protein
  • Serine
  • Tyrosine 3-Monooxygenase
  • Glutathione Transferase
  • RPS6KA1 protein, human
  • Ribosomal Protein S6 Kinases, 90-kDa
  • Cyclic AMP-Dependent Protein Kinases
  • Mitogen-Activated Protein Kinases