Structure and dynamic regulation of Abl kinases

J Biol Chem. 2013 Feb 22;288(8):5443-50. doi: 10.1074/jbc.R112.438382. Epub 2013 Jan 11.

Abstract

The c-abl proto-oncogene encodes a unique protein-tyrosine kinase (Abl) distinct from c-Src, c-Fes, and other cytoplasmic tyrosine kinases. In normal cells, Abl plays prominent roles in cellular responses to genotoxic stress as well as in the regulation of the actin cytoskeleton. Abl is also well known in the context of Bcr-Abl, the oncogenic fusion protein characteristic of chronic myelogenous leukemia. Selective inhibitors of Bcr-Abl, of which imatinib is the prototype, have had a tremendous impact on clinical outcomes in chronic myelogenous leukemia and revolutionized the field of targeted cancer therapy. In this minireview, we focus on the structural organization and dynamics of Abl kinases and how these features influence inhibitor sensitivity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Benzamides
  • Fusion Proteins, bcr-abl / biosynthesis*
  • Fusion Proteins, bcr-abl / physiology*
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Genes, abl / genetics*
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / enzymology
  • Models, Biological
  • Models, Chemical
  • Molecular Conformation
  • Mutation
  • Myristic Acid / chemistry
  • Piperazines / pharmacology
  • Protein Binding
  • Protein Structure, Tertiary
  • Pyrimidines / pharmacology
  • src Homology Domains

Substances

  • Benzamides
  • Piperazines
  • Pyrimidines
  • Myristic Acid
  • Imatinib Mesylate
  • Fusion Proteins, bcr-abl