Abstract
Despite years of investigation, the molecular mechanism responsible for regulation of the c-Abl tyrosine kinase has remained elusive. We now report inhibition of the catalytic activity of purified c-Abl in vitro, demonstrating that regulation is an intrinsic property of the molecule. We show that the interaction of the N-terminal 80 residues with the rest of the protein mediates autoregulation. This N-terminal "cap" is required to achieve and maintain inhibition, and its loss turns c-Abl into an oncogenic protein and contributes to deregulation of BCR-Abl.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Cell Line
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Fusion Proteins, bcr-abl / metabolism
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Genes, Reporter
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Humans
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Models, Molecular
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Molecular Sequence Data
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Precipitin Tests
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Protein Structure, Tertiary*
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Proto-Oncogene Proteins c-abl / antagonists & inhibitors*
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Proto-Oncogene Proteins c-abl / chemistry
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Proto-Oncogene Proteins c-abl / genetics
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Proto-Oncogene Proteins c-abl / metabolism*
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Recombinant Fusion Proteins / metabolism
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Regulatory Sequences, Nucleic Acid
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Schizosaccharomyces / genetics
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Schizosaccharomyces / metabolism
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Sequence Alignment
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Transfection
Substances
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Recombinant Fusion Proteins
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Fusion Proteins, bcr-abl
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Proto-Oncogene Proteins c-abl