Citation

  • Authors: Rotblat, B., Yizhar, O., Haklai, R., Ashery, U., Kloog, Y.
  • Year: 2006
  • Journal: Cancer Res 66 1974-81
  • Applications: in vitro / DNA / jetPEI
  • Cell types:
    1. Name: BHK-21
      Description: Hamster Syrian Kidney Fibroblast
      Known as: BHK21, BHK 21
    2. Name: COS-7
      Description: African green monkey kidney cells
      Known as: COS, COS7
    3. Name: HeLa
      Description: Human cervix epitheloid carcinoma cells

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.

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