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Updated: Aug 10, 2026

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
10:27

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

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

T Urano1, R Emkey, L A Feig

  • 1Department of Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.

The EMBO Journal
|February 15, 1996
PubMed

Insights

Ras-related GTPases (Ral) and their activator Ral-GDS are part of a distinct signaling pathway. This pathway, activated by RasH, potentiates oncogenic transformation, influencing RasH and Raf activities.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Oncogenesis

Background:

  • Ral proteins (RalA and RalB) are a distinct family of Ras-related GTPases.
  • Ral-GDS is the guanine nucleotide exchange factor that activates Ral proteins.
  • Previous studies indicated Ral-GDS binds activated RasH, R-Ras, and Rap1A via yeast two-hybrid systems.

Purpose of the Study:

  • To investigate the activation mechanism of Ral-GDS by Ras GTPases in mammalian cells.
  • To determine the role of Ral proteins in oncogenic transformation mediated by RasH and Raf.

Main Methods:

  • Mammalian cell-based assays to study GTPase binding and activation of Ral-GDS.
  • Analysis of oncogenic transformation induced by activated RalA, RasH, and Raf.
  • Utilized dominant-inhibitory RalA to assess its effect on RasH and Raf transformation.

Main Results:

  • While RasH, R-Ras, and Rap1A can bind Ral-GDS in mammalian cells, only RasH activates it.
  • Constitutively active RalA alone does not induce transformation but enhances RasH and Raf transforming activities.
  • A dominant-inhibitory RalA form suppresses the transforming activities of both RasH and Raf.

Conclusions:

  • The activation of Ral-GDS and its downstream target Ral represents a distinct signaling pathway from RasH.
  • This Ral pathway significantly potentiates oncogenic transformation driven by RasH and Raf.
  • Ral signaling is a crucial component in Ras-mediated oncogenesis.

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