The Ras-ERK and PI3K-mTOR pathways: cross-talk and compensation

Trends Biochem Sci. 2011 Jun;36(6):320-8. doi: 10.1016/j.tibs.2011.03.006. Epub 2011 Apr 30.


The Ras-extracellular signal-regulated kinase (Ras-ERK) and phosphatidylinositol 3-kinase-mammalian target of rapamycin (PI3K-mTOR) signaling pathways are the chief mechanisms for controlling cell survival, differentiation, proliferation, metabolism, and motility in response to extracellular cues. Components of these pathways were among the first to be discovered when scientists began cloning proto-oncogenes and purifying cellular kinase activities in the 1980s. Ras-ERK and PI3K-mTOR were originally modeled as linear signaling conduits activated by different stimuli, yet even early experiments hinted that they might intersect to regulate each other and co-regulate downstream functions. The extent of this cross-talk and its significance in cancer therapeutics are now becoming clear.

Publication types

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

MeSH terms

  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism*
  • ras Proteins / metabolism*


  • Phosphatidylinositol 3-Kinase
  • TOR Serine-Threonine Kinases
  • Extracellular Signal-Regulated MAP Kinases
  • ras Proteins