Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1

Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):7063-8. doi: 10.1073/pnas.93.14.7063.

Abstract

The Bcl-2 protein blocks programmed cell death (apoptosis) through an unknown mechanism. Previously we identified a Bcl-2 interacting protein BAG-1 that enhances the anti-apoptotic effects of Bcl-2. Like BAG-1, the serine/threonine protein kinase Raf-1 also can functionally cooperate with Bcl-2 in suppressing apoptosis. Here we show that Raf-1 and BAG-1 specifically interact in vitro and in yeast two-hybrid assays. Raf-1 and BAG-1 can also be coimmunoprecipitated from mammalian cells and from insect cells infected with recombinant baculoviruses encoding these proteins. Furthermore, bacterially-produced BAG-1 protein can increase the kinase activity of Raf-1 in vitro. BAG-1 also activates this mammalian kinase in yeast. These observations suggest that the Bcl-2 binding protein BAG-1 joins Ras and 14-3-3 proteins as potential activators of the kinase Raf-1.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis*
  • Carrier Proteins / metabolism*
  • Chlorocebus aethiops
  • Cloning, Molecular
  • DNA-Binding Proteins
  • Enzyme Activation
  • Glutathione Transferase
  • Humans
  • Kinetics
  • Mammals
  • Protein-Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-raf
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / metabolism
  • Spodoptera
  • Transcription Factors
  • Transfection

Substances

  • BCL2-associated athanogene 1 protein
  • Carrier Proteins
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins
  • Transcription Factors
  • Glutathione Transferase
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf