Autoinhibition of c-Abl

Cell. 2002 Jan 25;108(2):247-59. doi: 10.1016/s0092-8674(02)00623-2.


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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • 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


  • Recombinant Fusion Proteins
  • Fusion Proteins, bcr-abl
  • Proto-Oncogene Proteins c-abl