A role for the Ral guanine nucleotide dissociation stimulator in mediating Ras-induced transformation.
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.
White
M A
MA
Department of Cell Biology and Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9039, USA.
Vale
T
T
Camonis
J H
JH
Schaefer
E
E
Wigler
M H
MH
D016475:3T3 Cells; D000818:Animals; D002471:Cell Transformation, Neoplastic; D004789:Enzyme Activation; D019204:GTP-Binding Proteins / Q000502:physiology*; D051379:Mice; D015689:Oncogene Protein p21(ras) / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D020726:ral Guanine Nucleotide Exchange Factor; D020668:rap GTP-Binding Proteins
D020726:ral Guanine Nucleotide Exchange Factor; D011494:Protein Kinases; D019204:GTP-Binding Proteins; D015689:Oncogene Protein p21(ras); D020668:rap GTP-Binding Proteins