Regulating the regulator: post-translational modification of RAS

Nat Rev Mol Cell Biol. 2011 Dec 22;13(1):39-51. doi: 10.1038/nrm3255.


RAS proteins are monomeric GTPases that act as binary molecular switches to regulate a wide range of cellular processes. The exchange of GTP for GDP on RAS is regulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), which regulate the activation state of RAS without covalently modifying it. By contrast, post-translational modifications (PTMs) of RAS proteins direct them to various cellular membranes and, in some cases, modulate GTP-GDP exchange. Important RAS PTMs include the constitutive and irreversible remodelling of its carboxy-terminal CAAX motif by farnesylation, proteolysis and methylation, reversible palmitoylation, and conditional modifications, including phosphorylation, peptidyl-prolyl isomerisation, monoubiquitylation, diubiquitylation, nitrosylation, ADP ribosylation and glucosylation.

Publication types

  • Review

MeSH terms

  • Animals
  • GTPase-Activating Proteins / metabolism
  • Guanine Nucleotide Exchange Factors / metabolism
  • Humans
  • Mice
  • Protein Processing, Post-Translational*
  • ras Proteins / metabolism*


  • GTPase-Activating Proteins
  • Guanine Nucleotide Exchange Factors
  • ras Proteins