A Role for the Ral Guanine Nucleotide Dissociation Stimulator in Mediating Ras-induced Transformation

doi:10.1074/jbc.271.28.16439

A Role for the Ral Guanine Nucleotide Dissociation Stimulator in Mediating Ras-induced Transformation*

From the Department of Cell Biology and Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9039,
^§ INSERM U-248, Section de Recherche, Institut Curie, Paris 75231, France,
^¶ Signal Transduction, Promega Corporation, Madison, Wisconsin 53711, and
^∥ Cold Spring Harbor Laboratories, Cold Spring Harbor, New York 10021

^‡ To whom correspondence should be addressed:
Dept. of Cell Biology and Neuroscience, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75235-9039.
Tel.: 214-648-2861; Fax: 214-648-8694; E-mail: white08{at}utsw.swmed.edu

Abstract

Oncogenic Ras transforms cells through the activation of multiple downstream pathways mediated by separate effector molecules, one of which is Raf. Here we report the identification of a second ras-binding protein that can induce cellular transformation in parallel with activation of the Raf/mitogen-activated protein kinase cascade. The Ral guanine nucleotide dissociation stimulator (RalGDS) was isolated from a screen for Ras-binding proteins that specifically interact with a Ras effector-loop mutant, ras(12V,37G), that uncouples Ras from activation of Raf1. RalGDS, like ras(12V,37G), cooperates synergistically with mutationally activated Raf to induce foci of growth and morphologically transformed NIH 3T3 cells. RalGDS does not significantly enhance MAP kinase activation by activated Raf, suggesting that the cooperativity in focus formation is due to a distinct pathway acting downstream of Ras and parallel to Raf.

Footnotes

↵” American Cancer Society Research Professor.
↵* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
↵¹ The abbreviations used are:

MAP

mitogen-activated protein

MEK

mitogen-activated or extracellular signal-regulated kinase kinase

MBP

myelin basic protein

RalGDS

Ral guanine nucleotide dissociation stimulator.
- Received April 29, 1996.
- Revision received May 21, 1996.