A role for the Ral guanine nucleotide dissociation stimulator in mediating Ras-induced transformation

White, M. A., Vale, T., Camonis, J. H., Schaefer, E., Wigler, M. H. (July 1996) A role for the Ral guanine nucleotide dissociation stimulator in mediating Ras-induced transformation. J Biol Chem, 271 (28). pp. 16439-42. ISSN 0021-9258 (Print)

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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.

Item Type:	Paper
Uncontrolled Keywords:	3T3 Cells Animals Cell Transformation Neoplastic Enzyme Activation GTP-Binding Proteins physiology Mice Oncogene Protein p21(ras) physiology ras Protein Kinases metabolism ral Guanine Nucleotide Exchange Factor rap GTP Binding Proteins
Subjects:	bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > RAS bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > DNA binding protein bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > oncogene bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression
CSHL Authors:	Wigler, Michael H.
Communities:	CSHL labs > Wigler lab
Depositing User:	CSHL Librarian
Date:	12 July 1996
Date Deposited:	06 Apr 2012 14:51
Last Modified:	07 Nov 2016 20:17
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/25980

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