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

Authors

  • A. Lorentzen
  • A. Kinkhabwala
  • O. Rocks
  • N. Vartak
  • P.I. Bastiaens

Journal

  • Science Signaling

Citation

  • Sci Signal 3 (140): ra68

Abstract

  • 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.


DOI

doi:10.1126/scisignal.20001370