The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling

Lowenstein, E. J., Daly, R. J., Batzer, A. G., Li, W., Margolis, B., Lammers, R., Ullrich, A., Skolnik, E. Y., Bar-Sagi, D., Schlessinger, J. (August 1992) The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell, 70 (3). pp. 431-42. ISSN 0092-8674 (Print)0092-8674 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/1322798
DOI: 10.1016/0092-8674(92)90167-B

Abstract

A cDNA clone encoding a novel, widely expressed protein (called growth factor receptor-bound protein 2 or GRB2) containing one src homology 2 (SH2) domain and two SH3 domains was isolated. Immunoblotting experiments indicate that GRB2 associates with tyrosine-phosphorylated epidermal growth factor receptors (EGFRs) and platelet-derived growth factor receptors (PDGFRs) via its SH2 domain. Interestingly, GRB2 exhibits striking structural and functional homology to the C. elegans protein sem-5. It has been shown that sem-5 and two other genes called let-23 (EGFR like) and let-60 (ras like) lie along the same signal transduction pathway controlling C. elegans vulval induction. To examine whether GRB2 is also a component of ras signaling in mammalian cells, microinjection studies were performed. While injection of GRB2 or H-ras proteins alone into quiescent rat fibroblasts did not have mitogenic effect, microinjection of GRB2 together with H-ras protein stimulated DNA synthesis. These results suggest that GRB2/sem-5 plays a crucial role in a highly conserved mechanism for growth factor control of ras signaling.

Item Type: Paper
Uncontrolled Keywords: *Adaptor Proteins, Signal Transducing Amino Acid Sequence Animals Base Sequence Blotting, Northern Blotting, Western Caenorhabditis/genetics Cell Line DNA/biosynthesis/isolation & purification GRB2 Adaptor Protein Humans Mice Microinjections Molecular Sequence Data Oncogene Protein p21(ras)/*metabolism Phosphorylation Platelet-Derived Growth Factor/metabolism Protein-Tyrosine Kinases/*metabolism Proteins/chemistry/*genetics/metabolism Receptor, Epidermal Growth Factor/*metabolism Receptors, Cell Surface/*metabolism Receptors, Platelet-Derived Growth Factor Sequence Alignment *Signal Transduction
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > G protein > Ras
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > tyrosine kinase
CSHL Authors:
Communities: CSHL labs
Depositing User: Matt Covey
Date: 7 August 1992
Date Deposited: 01 Oct 2015 19:49
Last Modified: 01 Oct 2015 19:49
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31779

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