Research ArticleCell Biology

Regulation of Ras Localization by Acylation Enables a Mode of Intracellular Signal Propagation

Sci. Signal.  21 Sep 2010:
Vol. 3, Issue 140, pp. ra68
DOI: 10.1126/scisignal.20001370

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Ras Radio Waves

The Ras family of small guanosine triphosphatases (GTPases) has roles in cellular proliferation and is frequently mutated in tumors. Stimulation of cells with epidermal growth factor leads to the transient activation of H-Ras at the plasma membrane, followed by an echo of this activity at the Golgi. This distinct spatiotemporal activity profile suggests that the Golgi is a passive receiver of Ras signals from the plasma membrane. Lorentzen et al. performed quantitative imaging and mathematical modeling of cells in which binding of H-Ras to GDP or GTP was decoupled from the acylation cycle that maintains its spatial organization. Regulation of H-Ras binding to GDP or GTP occurred only at the plasma membrane and not at the Golgi. Furthermore, the acylation cycle delivered active H-Ras from the plasma membrane to the Golgi, as well as from the endoplasmic reticulum to the Golgi; this latter delivery route enabled sustained H-Ras activity at the Golgi after the initial activation echo. Thus, the amount of active Ras at the Golgi is determined by activation of Ras at the plasma membrane and the endoplasmic reticulum, and the acylation cycle serves to relay activated Ras between subcellular compartments.