Bcl-2 targets the protein kinase Raf-1 to mitochondria.
A green fluorescent protein (GFP)-Raf-1 fusion protein was used to show that Bcl-2 can target this kinase to mitochondria. Active Raf-1 fused with targeting sequences from an outer mitochondrial membrane protein protected cells from apoptosis and resulted in phosphorylation of BAD, a proapoptotic Bcl-2 homolog. Plasma membrane-targeted Raf-1 did not ... protect from apoptosis and resulted in phosphorylation of ERK-1 and ERK-2. Untargeted active Raf-1 improved Bcl-2-mediated resistance to apoptosis, whereas a kinase-inactive Raf-1 mutant abrogated apoptosis suppression by Bcl-2. Bcl-2 can therefore target Raf-1 to mitochondrial membranes, allowing this kinase to phosphorylate BAD or possibly other protein substrates involved in apoptosis regulation.
Mesh Terms:
Apoptosis, Biological Transport, Calcium-Calmodulin-Dependent Protein Kinases, Carrier Proteins, Cell Compartmentation, Cell Membrane, Cells, Cultured, Green Fluorescent Proteins, Luminescent Proteins, Mitochondria, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, Phosphorylation, Protein Binding, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Proto-Oncogene Proteins c-raf, Recombinant Fusion Proteins, Signal Transduction, Staurosporine, Subcellular Fractions, Transfection, bcl-Associated Death Protein
Apoptosis, Biological Transport, Calcium-Calmodulin-Dependent Protein Kinases, Carrier Proteins, Cell Compartmentation, Cell Membrane, Cells, Cultured, Green Fluorescent Proteins, Luminescent Proteins, Mitochondria, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, Phosphorylation, Protein Binding, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-bcl-2, Proto-Oncogene Proteins c-raf, Recombinant Fusion Proteins, Signal Transduction, Staurosporine, Subcellular Fractions, Transfection, bcl-Associated Death Protein
Cell
Date: Nov. 15, 1996
PubMed ID: 8929532
View in: Pubmed Google Scholar
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