Ral-GTPases mediate a distinct downstream signaling pathway from Ras that facilitates cellular transformation

EMBO J. 1996 Feb 15;15(4):810-6.


Ral proteins (RalA and RalB) comprise a distinct family of Ras-related GTPases (Feig and Emkey, 1993). Recently, Ral-GDS, the exchange factor that activates Ral proteins, has been shown to bind specifically to the activated forms of RasH, R-Ras and Rap1A, in the yeast two-hybrid system. Here we demonstrate that although all three GTPases have the capacity to bind Ral-GDS in mammalian cells, only RasH activates Ral-GDS. Furthermore, although constitutively activated Ra1A does not induce oncogenic transformation on its own, its expression enhances the transforming activities of both RasH and Raf. Finally, a dominant inhibitory form of RalA suppresses the transforming activities of both RasH and Raf. These results demonstrate that activation of Ral-GDS and thus its target, Ral, constitutes a distinct downstream signaling pathway from RasH that potentiates oncogenic transformation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Cell Division
  • Cell Transformation, Neoplastic*
  • Chlorocebus aethiops
  • Epitopes
  • GTP-Binding Proteins / physiology*
  • Mice
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / immunology
  • Protein-Serine-Threonine Kinases / physiology
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-raf
  • Proto-Oncogene Proteins p21(ras) / physiology*
  • Signal Transduction
  • ral GTP-Binding Proteins


  • Epitopes
  • Peptides
  • Proto-Oncogene Proteins
  • Ralb protein, rat
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • GTP-Binding Proteins
  • Proto-Oncogene Proteins p21(ras)
  • ral GTP-Binding Proteins