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PMID:1322798
| Citation |
Lowenstein, EJ, Daly, RJ, Batzer, AG, Li, W, Margolis, B, Lammers, R, Ullrich, A, Skolnik, EY, Bar-Sagi, D and Schlessinger, J (1992) The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell 70:431-42 |
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| 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. |
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| Keywords |
Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Animals; Base Sequence; Blotting, Northern; Blotting, Western; Caenorhabditis/genetics; Cell Line; DNA/biosynthesis; DNA/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; Proteins/genetics; Proteins/metabolism; Receptor, Epidermal Growth Factor/metabolism; Receptors, Cell Surface/metabolism; Receptors, Platelet-Derived Growth Factor; Sequence Alignment; Signal Transduction |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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