Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery

Cell. 1997 Oct 17;91(2):231-41. doi: 10.1016/s0092-8674(00)80405-5.

Abstract

Growth factors can promote cell survival by activating the phosphatidylinositide-3'-OH kinase and its downstream target, the serine-threonine kinase Akt. However, the mechanism by which Akt functions to promote survival is not understood. We show that growth factor activation of the PI3'K/Akt signaling pathway culminates in the phosphorylation of the BCL-2 family member BAD, thereby suppressing apoptosis and promoting cell survival. Akt phosphorylates BAD in vitro and in vivo, and blocks the BAD-induced death of primary neurons in a site-specific manner. These findings define a mechanism by which growth factors directly inactivate a critical component of the cell-intrinsic death machinery.

Publication types

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

MeSH terms

  • 3T3 Cells / physiology
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / metabolism*
  • Cell Death / drug effects
  • Cell Death / physiology
  • Cell Survival / physiology
  • Insulin-Like Growth Factor I / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Neurons / cytology*
  • Neurons / enzymology*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Serine / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • bcl-Associated Death Protein

Substances

  • Bad protein, mouse
  • Carrier Proteins
  • Proto-Oncogene Proteins
  • bcl-Associated Death Protein
  • Serine
  • Insulin-Like Growth Factor I
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt