Oncogenic K-Ras requires activation for enhanced activity

Oncogene. 2014 Jan 23;33(4):532-5. doi: 10.1038/onc.2012.619. Epub 2013 Jan 21.


Oncogenic Ras mutations are widely considered to be locked in a permanent 'On' state and 'constitutively active'. Yet, many healthy people have cells possessing mutant Ras without apparent harm, and in animal models mutant Ras causes transformation only after upregulation of Ras activity. Here, we demonstrate that oncogenic K-Ras is not constitutively active but can be readily activated by upstream stimulants to lead to prolonged strong Ras activity. These data indicate that in addition to targeting K-Ras downstream effectors, interventions to reduce K-Ras activation may have important cancer-preventive value, especially in patients with oncogenic Ras mutations. As other small G proteins are regulated in a similar manner, this concept is likely to apply broadly to the entire Ras family of molecules.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Electrophoresis, Polyacrylamide Gel
  • Genes, ras / genetics
  • Humans
  • Mice
  • Mice, Mutant Strains
  • Mutation
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Proto-Oncogene Proteins p21(ras) / metabolism


  • Hras protein, mouse
  • Proto-Oncogene Proteins p21(ras)