Regulation of Ras localization by acylation enables a mode of intracellular signal propagation

Sci Signal. 2010 Sep 21;3(140):ra68. doi: 10.1126/scisignal.20001370.


Growth factor stimulation generates transient H-Ras activity at the plasma membrane but sustained activity at the Golgi. Two overlapping regulatory networks control compartmentalized H-Ras activity: the guanosine diphosphate-guanosine triphosphate cycle and the acylation cycle, which constitutively traffics Ras isoforms that can be palmitoylated between intracellular membrane compartments. Quantitative imaging of H-Ras activity after decoupling of these networks revealed regulation of H-Ras activity at the plasma membrane but not at the Golgi. Nevertheless, upon stimulation with epidermal growth factor, Ras activity at the Golgi displayed a pulse-like profile similar to that at the plasma membrane but also remained high after the initial stimulus. A compartmental model that included the acylation cycle and H-Ras regulation at the plasma membrane accounted for the pulse-like profile of H-Ras activity at the Golgi but implied that sustained H-Ras activity at the Golgi required H-Ras activation at an additional compartment, which we experimentally determined to be the endoplasmic reticulum. Thus, in addition to maintaining the localization of Ras, the acylation cycle underlies a previously unknown form of signal propagation similar to radio transmission in its generation of a constitutive Ras "carrier wave" that transmits Ras activity between subcellular compartments.

MeSH terms

  • Acylation
  • Animals
  • Cell Compartmentation / physiology
  • Cell Line
  • Cell Membrane / metabolism*
  • Dogs
  • Epidermal Growth Factor / metabolism
  • Golgi Apparatus / metabolism*
  • Microscopy, Fluorescence / methods
  • Models, Biological*
  • Signal Transduction / physiology*
  • ras Proteins / metabolism*


  • Epidermal Growth Factor
  • ras Proteins