Skip to content


  • Research news
  • Open Access

A protein kinase switch

Genome Biology20001:spotlight-20000929-01

  • Published:


  • Nucleotide
  • Tyrosine
  • Protein Kinase
  • Tyrosine Kinase
  • Kinase Inhibitor

Kinase inhibitors are plagued by a lack of specificity. Now in the 21 September Nature Bishop et al. tackle the problem by building on their earlier work, in which they modified the ATP-binding sites of Src-family tyrosine kinases to accept either nucleotide analogs or modified kinase inhibitors. In the new work the researchers mutate kinases from four distinct kinase families by replacing a bulky residue with a small residue. This change provides enough room for the binding of inhibitor analogs, which are larger than their parent inhibitors and thus do not inhibit wild-type kinases (Nature 2000, 407:395-401). The in vivo specificity is demonstrated using expression arrays. Most kinases contain a bulky residue analogous to the one mutated in this study, and thus should be amenable to the kinase-sensitization strategy.


  1. Exploiting chemical libraries, structure, and genomics in the search for kinase inhibitors.Google Scholar
  2. Nature, []
  3. Engineering Src family protein kinases with unnatural nucleotide specificity.Google Scholar


© BioMed Central Ltd 2000