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| Item Type: | Article |
|---|---|
| Title: | Regulation of Ras localization by acylation enables a mode of intracellular signal propagation |
| Creators Name: | Lorentzen, A., Kinkhabwala, A., Rocks, O., 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 |
| ISSN: | 1937-9145 |
| Publisher: | American Association for the Advancement of Science |
| Volume: | 3 |
| Number: | 140 |
| 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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