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)
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: | https://repository.cshl.edu/id/eprint/31779 |
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