Autoinhibition of c-Abl

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 th...

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Bibliographic Details
Published inCell Vol. 108; no. 2; pp. 247 - 259
Main Authors Pluk, Helma, Dorey, Karel, Superti-Furga, Giulio
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 25.01.2002
Subjects
Amino Acid Sequence
c-Abl protein
Cell Line
Fusion Proteins, bcr-abl - metabolism
Genes, Reporter
Humans
Models, Molecular
Molecular Sequence Data
Precipitin Tests
Protein Structure, Tertiary
Proto-Oncogene Proteins c-abl - antagonists & inhibitors
Proto-Oncogene Proteins c-abl - chemistry
Proto-Oncogene Proteins c-abl - genetics
Proto-Oncogene Proteins c-abl - metabolism
Recombinant Fusion Proteins - metabolism
Regulatory Sequences, Nucleic Acid
Schizosaccharomyces - genetics
Schizosaccharomyces - metabolism
Sequence Alignment
Transfection
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Summary: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.
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ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(02)00623-2