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Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14-3-3 not BCL-X(L)

Extracellular survival factors alter a cell's susceptibility to apoptosis, often through posttranslational mechanisms. However, no consistent relationship has been established between such survival signals and the BCL-2 family, where the balance of death agonists versus antagonists determines susceptibility. One distant member, BAD, heterodimerizes with BCL-X(L) or BCL-2, neutralizing their protective effect and promoting cell death. In the presence of survival factor IL-3, cells phosphorylated BAD on two serine residues embedded in 14-3-3 consensus binding sites. Only the nonphosphorylated BAD heterodimerized with BCL-X(L) at membrane sites to promote cell death. Phosphorylated BAD was sequestered in the cytosol bound to 14-3-3. Substitution of serine phosphorylation sites further enhanced BAD's death-promoting activity. The rapid phosphorylation of BAD following IL-3 connects a proximal survival signal with the BCL-2 family, modulating this checkpoint for apoptosis.

Pubmed ID: 8929531


  • Zha J
  • Harada H
  • Yang E
  • Jockel J
  • Korsmeyer SJ



Publication Data

November 15, 1996

Associated Grants

  • Agency: NCI NIH HHS, Id: R01 CA50239

Mesh Terms

  • 14-3-3 Proteins
  • Amino Acid Sequence
  • Carrier Proteins
  • Cell Death
  • Cell Survival
  • Cytosol
  • Dimerization
  • Interleukin-3
  • Membranes
  • Models, Biological
  • Molecular Sequence Data
  • Phosphorylation
  • Protein Binding
  • Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Serine
  • Signal Transduction
  • Tyrosine 3-Monooxygenase
  • bcl-Associated Death Protein
  • bcl-X Protein