Structure and physiology of the RET receptor tyrosine kinase

Cold Spring Harb Perspect Biol. 2013 Feb 1;5(2):a009134. doi: 10.1101/cshperspect.a009134.


The identification of the ret oncogene by Masahide Takahashi and Geoffrey Cooper in 1985 was both serendipitous and paradigmatic ( Takahashi et al. 1985). By transfecting total DNA from a human lymphoma into mouse NIH3T3 cells, they obtained one clone, which in secondary transformants yielded more than 100-fold improvement in transformation efficiency. Subsequent investigations revealed that the ret oncogene was not present as such in the primary lymphoma, but was derived by DNA rearrangement during transfection from normal human sequences of the ret locus. At the time, activation by DNA rearrangement had not been previously described for a transforming gene with the NIH3T3 transfection assay. The discovery of ret opened a field of study that has had a profound impact in cancer research, developmental biology, and neuroscience, and that continues to yield surprises and important insights to this day.

Publication types

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

MeSH terms

  • Animals
  • Cell Transformation, Neoplastic
  • Evolution, Molecular
  • Gene Rearrangement
  • Humans
  • Kidney / embryology
  • Ligands
  • Mice
  • NIH 3T3 Cells
  • Nervous System / embryology
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-ret / chemistry
  • Proto-Oncogene Proteins c-ret / physiology*
  • Signal Transduction


  • Ligands
  • Proto-Oncogene Proteins c-ret