beta -Amyloid peptide-induced apoptosis regulated by a novel protein containing a g protein activation module.
Degeneration of neurons in Alzheimer's disease is mediated by beta-amyloid peptide by diverse mechanisms, which include a putative apoptotic component stimulated by unidentified signaling events. This report describes a novel beta-amyloid peptide-binding protein (denoted BBP) containing a G protein-coupling module. BBP is one member of a family of three proteins ... containing this conserved structure. The BBP subtype bound human beta-amyloid peptide in vitro with high affinity and specificity. Expression of BBP in cell culture induced caspase-dependent vulnerability to beta-amyloid peptide toxicity. Expression of a signaling-deficient dominant negative BBP mutant suppressed sensitivity of human Ntera-2 neurons to beta-amyloid peptide mediated toxicity. These findings suggest that BBP is a target of neurotoxic beta-amyloid peptide and provide new insight into the molecular pathophysiology of Alzheimer's disease.
Mesh Terms:
Alzheimer Disease, Amino Acid Sequence, Amyloid beta-Peptides, Apoptosis, Binding Sites, Binding, Competitive, Blotting, Northern, Brain, Carrier Proteins, Caspases, Cell Line, Cell Membrane, Cells, Cultured, Conserved Sequence, DNA, Complementary, Dose-Response Relationship, Drug, GTP-Binding Proteins, Gene Library, Humans, Immunoblotting, In Situ Hybridization, Kinetics, Models, Biological, Molecular Sequence Data, Mutation, Neurons, Peptides, Protein Binding, Protein Biosynthesis, Protein Structure, Tertiary, Recombinant Proteins, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Amino Acid, Signal Transduction, Tissue Distribution, Two-Hybrid System Techniques
Alzheimer Disease, Amino Acid Sequence, Amyloid beta-Peptides, Apoptosis, Binding Sites, Binding, Competitive, Blotting, Northern, Brain, Carrier Proteins, Caspases, Cell Line, Cell Membrane, Cells, Cultured, Conserved Sequence, DNA, Complementary, Dose-Response Relationship, Drug, GTP-Binding Proteins, Gene Library, Humans, Immunoblotting, In Situ Hybridization, Kinetics, Models, Biological, Molecular Sequence Data, Mutation, Neurons, Peptides, Protein Binding, Protein Biosynthesis, Protein Structure, Tertiary, Recombinant Proteins, Reverse Transcriptase Polymerase Chain Reaction, Sequence Homology, Amino Acid, Signal Transduction, Tissue Distribution, Two-Hybrid System Techniques
J. Biol. Chem.
Date: Jun. 01, 2001
PubMed ID: 11278849
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