Ras and its signals diffuse through the cell on randomly moving nanoparticles

Barak Rotblat, Ofer Yizhar, Roni Haklai, Uri Ashery, Yoel Kloog

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1974-1981
Number of pages8
JournalCancer Research
Volume66
Issue number4
DOIs
StatePublished - 15 Feb 2006
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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