Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt

Science. 1997 Oct 24;278(5338):687-9. doi: 10.1126/science.278.5338.687.

Abstract

BAD is a distant member of the Bcl-2 family that promotes cell death. Phosphorylation of BAD prevents this. BAD phosphorylation induced by interleukin-3 (IL-3) was inhibited by specific inhibitors of phosphoinositide 3-kinase (PI 3-kinase). Akt, a survival-promoting serine-threonine protein kinase, was activated by IL-3 in a PI 3-kinase-dependent manner. Active, but not inactive, forms of Akt were found to phosphorylate BAD in vivo and in vitro at the same residues that are phosphorylated in response to IL-3. Thus, the proapoptotic function of BAD is regulated by the PI 3-kinase-Akt pathway.

Publication types

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

MeSH terms

  • Androstadienes / pharmacology
  • Animals
  • Apoptosis
  • Carrier Proteins / metabolism*
  • Cell Line
  • Chromones / pharmacology
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Interleukin-3 / pharmacology*
  • Mice
  • Morpholines / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Phosphoserine / metabolism
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Wortmannin
  • bcl-Associated Death Protein
  • bcl-X Protein

Substances

  • Androstadienes
  • BAD protein, human
  • BCL2L1 protein, human
  • Bad protein, mouse
  • Bcl2l1 protein, mouse
  • Carrier Proteins
  • Chromones
  • Enzyme Inhibitors
  • Interleukin-3
  • Morpholines
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins
  • bcl-Associated Death Protein
  • bcl-X Protein
  • Phosphoserine
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Wortmannin