Ras binding opens c-Raf to expose the docking site for mitogen-activated protein kinase kinase

EMBO Rep. 2005 Mar;6(3):251-5. doi: 10.1038/sj.embor.7400349.


A key signalling molecule, c-Raf, is situated downstream from Ras and upstream from the mitogen-activated protein kinase kinase (MEK). We studied the mechanism underlying the signal transduction from Ras to MEK by using probes based on the principle of fluorescence resonance energy transfer. In agreement with previous models, it was found that c-Raf adopted two conformations: open active and closed inactive. Ras binding induced the c-Raf transition from closed to open conformation, which enabled c-Raf to bind to MEK. In the presence of a cytosolic Ras mutant, c-Raf bound to, but failed to phosphorylate, MEK in the cytoplasm. In contrast, the cytosolic Ras mutant significantly enhanced MEK phosphorylation by a membrane-targeted c-Raf. These results demonstrated the essential role of Ras-induced conformational change in MEK activation by c-Raf.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Substitution
  • Animals
  • Binding Sites
  • Cell Line
  • Chlorocebus aethiops
  • Humans
  • Mitogen-Activated Protein Kinase Kinases / metabolism*
  • Mutation / genetics
  • Protein Binding
  • Protein Conformation
  • Proto-Oncogene Proteins c-raf / chemistry*
  • Proto-Oncogene Proteins c-raf / genetics
  • Proto-Oncogene Proteins c-raf / metabolism*
  • ras Proteins / metabolism*


  • Proto-Oncogene Proteins c-raf
  • Mitogen-Activated Protein Kinase Kinases
  • ras Proteins