Deceiving appearances: signaling by "dead" and "fractured" receptor protein-tyrosine kinases

Bioessays. 2001 Jan;23(1):69-76. doi: 10.1002/1521-1878(200101)23:1<69::AID-BIES1009>3.0.CO;2-K.


The mechanisms by which most receptor protein-tyrosine kinases (RTKs) transmit signals are now well established. Binding of ligand results in the dimerization of receptor monomers followed by transphosphorylation of tyrosine residues within the cytoplasmic domains of the receptors. This tidy picture has, however, some strange characters lurking around the edges. Cases have now been identified in which RTKs lack kinase activity, but, despite being "dead" appear to have roles in signal transduction. Even stranger are the cases in which genes encoding RTKs produce protein products consisting of only a portion of the kinase domain. At least one such "fractured" RTK appears to be involved in signal transduction. Here we describe how these strange molecules might function and discuss the questions associated with their evolution. BioEssays 23:69-76, 2001.

Publication types

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

MeSH terms

  • Animals
  • Evolution, Molecular
  • Humans
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins c-kit / genetics
  • Proto-Oncogene Proteins c-kit / metabolism*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Receptor, ErbB-3 / genetics
  • Receptor, ErbB-3 / metabolism*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Signal Transduction / physiology*


  • Hinterteil protein, Hydra vulgaris
  • Receptors, Cell Surface
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-kit
  • RYK protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, ErbB-3