Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1.
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.
Mesh Terms:
Animals, Apoptosis, Carrier Proteins, Cercopithecus aethiops, Cloning, Molecular, DNA-Binding Proteins, Enzyme Activation, Glutathione Transferase, Humans, Kinetics, Mammals, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Proto-Oncogene Proteins c-raf, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Spodoptera, Transcription Factors, Transfection
Animals, Apoptosis, Carrier Proteins, Cercopithecus aethiops, Cloning, Molecular, DNA-Binding Proteins, Enzyme Activation, Glutathione Transferase, Humans, Kinetics, Mammals, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Proto-Oncogene Proteins c-raf, Recombinant Fusion Proteins, Saccharomyces cerevisiae, Spodoptera, Transcription Factors, Transfection
Proc. Natl. Acad. Sci. U.S.A.
Date: Jul. 09, 1996
PubMed ID: 8692945
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