Grb2 mediates the EGF-dependent activation of guanine nucleotide exchange on Ras

Gale, N. W., Kaplan, S., Lowenstein, E. J., Schlessinger, J., Bar-Sagi, D. (May 1993) Grb2 mediates the EGF-dependent activation of guanine nucleotide exchange on Ras. Nature, 363 (6424). pp. 88-92. ISSN 0028-0836 (Print)

URL: http://www.ncbi.nlm.nih.gov/pubmed/8386805
DOI: 10.1038/363088a0

Abstract

Activation of receptor tyrosine kinases such as those for epidermal growth factor (EGF), platelet-derived growth factor, or nerve growth factor converts the inactive, GDP-bound form of Ras to the active, GTP-bound form, and a dominant negative mutant of Ras interferes with signalling from such receptors. The mechanisms by which receptor tyrosine kinases and Ras are coupled, however, are not well understood. Many cytoplasmic proteins regulated by such receptors contain Src-homology (SH) 2 and 3 domains, and the SH2- and SH3-containing protein Grb2, like its homologue from Caenorhabditis elegans, Sem-5, appears to play an important role in the control of Ras by receptor tyrosine kinases. Here we show that overexpression of Grb2 potentiates the EGF-induced activation of Ras and mitogen-activated protein kinase by enhancing the rate of guanine nucleotide exchange on Ras. Cellular Grb2 appears to form a complex with a guanine-nucleotide-exchange factor for Ras, which binds to the ligand-activated EGF receptor, allowing the tyrosine kinase to modulate Ras activity.

Item Type: Paper
Uncontrolled Keywords: 3T3 Cells Adaptor Proteins, Signal Transducing Animals Ca(2+)-Calmodulin Dependent Protein Kinase Enzyme Activation Epidermal Growth Factor/ metabolism GRB2 Adaptor Protein GTP-Binding Proteins/ metabolism GTPase-Activating Proteins Guanine Nucleotides/ metabolism Humans Mice Protein Kinases/metabolism Protein-Tyrosine Kinase/ metabolism Proteins/ metabolism Receptor, Epidermal Growth Factor/metabolism Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. ras GTPase-Activating Proteins
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > GTPase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > epidermal growth factor
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > GTP binding protein
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > G protein > Ras
CSHL Authors:
Communities: CSHL labs
Depositing User: Matt Covey
Date: 6 May 1993
Date Deposited: 11 Apr 2016 19:44
Last Modified: 11 Apr 2016 19:44
Related URLs:
URI: http://repository.cshl.edu/id/eprint/32570

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