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

Item Type:Article
Title:Regulation of Ras localization by acylation enables a mode of intracellular signal propagation
Creators Name:Lorentzen, A. and Kinkhabwala, A. and Rocks, O. and Vartak, N. and Bastiaens, P.I.
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.
Keywords:Acylation, Cell Compartmentation, Cell Line, Cell Membrane, Epidermal Growth Factor, Golgi Apparatus, Fluorescence Microscopy, Biological Models, Signal Transduction, ras Proteins, Animals, Dogs
Source:Science Signaling
Publisher:American Association for the Advancement of Science
Page Range:ra68
Date:21 September 2010
Official Publication:https://doi.org/10.1126/scisignal.20001370
PubMed:View item in PubMed

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