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Sci. STKE, 1 October 2002
Vol. 2002, Issue 152, p. pe41
[DOI: 10.1126/scisignal.1522002pe41]

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Insider Information: How Palmitoylation of Ras Makes It a Signaling Double Agent

Luc G. Berthiaume*

Department of Cell Biology, MSB-555, University of Alberta, Edmonton, Alberta, Canada T6G 2S2.

Abstract: Ras small guanosine triphosphatases (GTPases) are involved in the regulation of cell growth, differentiation, and survival and are mutated in as many as 30% of human cancers. These proto-oncogenic GTPases are mostly involved in the activation of signaling cascades downstream from growth factor receptors and lead to transcriptional activation of specific genes. Because of a complex series of posttranslational COOH-terminal modifications, Ras proteins are found on various intracellular membranes, in addition to the plasma membrane. Using a novel fluorescent probe monitoring GTP-bound Ras in live cells (GFP-Raf-1-RBS), Golgi-associated H-Ras was shown to be activated in situ after growth factor stimulation, with kinetics distinct from that of H-Ras activation at the plasma membrane. Furthermore and also noteworthy, an oncogenic H-Ras chimera that was tethered to the endoplasmic reticulum activated the extracellular signal-regulated kinase (ERK) and Akt pathways preferentially, whereas a Golgi-tethered oncogenic H-Ras chimera activated predominantly the Jun-NH2-terminal kinase (JNK) pathway. Thus, the subcellular localization of Ras influenced which downstream effector pathways were engaged. The activation of Golgi-H-Ras may be mediated by second messengers through the action of a Golgi-localized guanine nucleotide exchange factor, Ras-GRP.

*Contact information. Telephone, 780-492-5146; fax, 780-492-0450; e-mail, luc.berthiaume{at}ualberta.ca

Citation: L. G. Berthiaume, Insider Information: How Palmitoylation of Ras Makes It a Signaling Double Agent. Sci. STKE 2002, pe41 (2002).

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