Abstract
MANY of the actions of receptor tyrosine kinases are mediated by the protein Ras1–5, including the activation of various downstream serine/threonine kinases and the stimulation of growth and differentiation6–12. The human protein Grb2 binds to ligand-activated growth factor receptors and downstream effector proteins through its Src-homology (SH) domains SH2 and SH3, respectively13,14, and like its homologue from Caenorhabditis elegans, Sem-5, apparently forms part of a highly conserved pathway by which these receptors can control Ras activity15–18. 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 sevenless19,20. Moreover, a synthetic 10-amino-acid peptide containing the sequence PPVPPR specifically blocks the interaction. These results indicate that the Grbl/hSos1 complex couples activated EGF receptor to Ras signalling.
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Li, N., Batzer, A., Daly, R. et al. Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling. Nature 363, 85–88 (1993). https://doi.org/10.1038/363085a0
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DOI: https://doi.org/10.1038/363085a0
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