This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Rotblat, B. Articles by Kloog, Y. Search for Related Content PubMed PubMed Citation Articles by Rotblat, B. Articles by Kloog, Y.

Ras and Its Signals Diffuse through the Cell on Randomly Moving Nanoparticles

Department of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel

Requests for reprints: Yoel Kloog, Department of Neurobiochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, 69978 Tel Aviv, Israel. Phone: 972-3-640-9699; Fax: 972-3-640-7643; E-mail: yoelk{at}tauex.tau.ac.il.

Spatiotemporal modulation of Ras signaling from different intracellular compartments requires mechanisms allowing Ras and its signals to navigate across cells. Here, we describe one mechanism by which clusters of palmitoylated H-Ras and N-Ras isoforms but not nonpalmitoylated K-Ras diffuse through the cytoplasm, independently of ATP, on fast, randomly moving, small cytosolic nanoparticles ("rasosomes"). Rasosomes forced to diffuse out of live cells and trapped by Ras antibody beads appear as round structures of 80- to 100-nm diameter. Association of H-Ras with rasosomes requires Ras palmitoylation and the hypervariable sequence (hvr) upstream of the palmitoylated cysteines. H-Ras hvr mutants that fail to interact with rasosomes are biologically inactive. Epidermal growth factor stimulation rapidly increases active H-Ras-GTP and phosphorylated extracellular signal-regulated kinase (ERK) on rasosomes. Similarly, rasosomes carrying H-Ras(G12V) but not H-Ras are loaded with active ERK. Thus, the rasosome represents a hitherto unknown particle that enables Ras signal information to spread rapidly across cells. (Cancer Res 2006; 66(4): 1974-81)

This article has been cited by other articles:

				N. Porat-Shliom, Y. Kloog, and J. G. Donaldson A Unique Platform for H-Ras Signaling Involving Clathrin-independent Endocytosis Mol. Biol. Cell, March 1, 2008; 19(3): 765 - 775. [Abstract] [Full Text] [PDF]

				A. J. Laude and I. A. Prior Palmitoylation and localisation of RAS isoforms are modulated by the hypervariable linker domain J. Cell Sci., February 15, 2008; 121(4): 421 - 427. [Abstract] [Full Text] [PDF]

				H. Zheng, J. McKay, and J. E. Buss H-Ras Does Not Need COP I- or COP II-dependent Vesicular Transport to Reach the Plasma Membrane J. Biol. Chem., August 31, 2007; 282(35): 25760 - 25768. [Abstract] [Full Text] [PDF]