Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. STKE, 1 October 2002
Vol. 2002, Issue 152, p. pe41
[DOI: 10.1126/stke.2002.152.pe41]

PERSPECTIVES

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).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Driven to Death: Inhibition of Farnesylation Increases Ras Activity in Osteosarcoma and Promotes Growth Arrest and Cell Death.
M. Geryk-Hall, Y. Yang, and D. P. M. Hughes (2010)
Mol. Cancer Ther. 9, 1111-1119
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882