GTP-dependent segregation of H-ras from lipid rafts is required for biological activity

Nat Cell Biol. 2001 Apr;3(4):368-75. doi: 10.1038/35070050.


Different sites of plasma membrane attachment may underlie functional differences between isoforms of Ras. Here we show that palmitoylation and farnesylation targets H-ras to lipid rafts and caveolae, but that the interaction of H-ras with these membrane subdomains is dynamic. GTP-loading redistributes H-ras from rafts into bulk plasma membrane by a mechanism that requires the adjacent hypervariable region of H-ras. Release of H-ras-GTP from rafts is necessary for efficient activation of Raf. By contrast, K-ras is located outside rafts irrespective of bound nucleotide. Our studies identify a novel protein determinant that is required for H-ras function, and show that the GTP/GDP state of H-ras determines its lateral segregation on the plasma membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Membrane / metabolism
  • Cricetinae
  • Enzyme Activation
  • Guanosine Triphosphate / metabolism*
  • Lipid Metabolism
  • Membrane Microdomains / metabolism*
  • Microscopy, Immunoelectron
  • Proto-Oncogene Proteins c-raf / metabolism
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*


  • Recombinant Fusion Proteins
  • Guanosine Triphosphate
  • Proto-Oncogene Proteins c-raf
  • Proto-Oncogene Proteins p21(ras)