Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling - PubMed (original) (raw)
. 1993 May 6;363(6424):85-8.
doi: 10.1038/363085a0.
Affiliations
- PMID: 8479541
- DOI: 10.1038/363085a0
Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling
N Li et al. Nature. 1993.
Abstract
Many of the actions of receptor tyrosine kinases are mediated by the protein Ras, including the activation of various downstream serine/threonine kinases and the stimulation of growth and differentiation. The human protein Grb2 binds to ligand-activated growth factor receptors and downstream effector proteins through its Src-homology (SH) domains SH2 and SH3, respectively, and like its homologue from Caenorhabditis elegans, Sem-5, apparently forms part of a highly conserved pathway by which these receptors can control Ras activity. Here we show that the SH3 domains of Grb2 bind to the carboxy-terminal part of hSos1, the human homologue of the Drosophila guanine-nucleotide-releasing factor for Ras, which is essential for control of Ras activity by epidermal growth factor receptor and sevenless. Moreover, a synthetic 10-amino-acid peptide containing the sequence PPVPPR specifically blocks the interaction. These results indicate that the Grb2/hSos1 complex couples activated EGF receptor to Ras signalling.
Comment in
- Signal transduction. How receptors turn Ras on.
McCormick F. McCormick F. Nature. 1993 May 6;363(6424):15-6. doi: 10.1038/363015a0. Nature. 1993. PMID: 8479530 No abstract available.
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