Extracellular assembly and activation principles of oncogenic class III receptor tyrosine kinases

Nat Rev Cancer. 2012 Nov;12(11):753-66. doi: 10.1038/nrc3371. Epub 2012 Oct 18.


Intracellular signalling cascades initiated by class III receptor tyrosine kinases (RTK-IIIs) and their cytokine ligands contribute to haematopoiesis and mesenchymal tissue development. They are also implicated in a wide range of inflammatory disorders and cancers. Recent snapshots of RTK-III ectodomains in complex with cognate cytokines have revealed timely insights into the structural determinants of RTK-III activation, evolution and pathology. Importantly, candidate 'driver' and 'passenger' mutations that have been identified in RTK-IIIs can now be collectively mapped for the first time to structural scaffolds of the corresponding RTK-III ectodomains. Such insights will generate a renewed interest in dissecting the mechanistic effects of such mutations and their therapeutic relevance.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Transformation, Neoplastic
  • Cytokines / metabolism*
  • Hematopoiesis / physiology
  • Humans
  • Ligands
  • Mutation
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Signal Transduction


  • Cytokines
  • Ligands
  • Receptor Protein-Tyrosine Kinases