Li, N., Batzer, A., Daly, R., Yajnik, V., Skolnik, E., Chardin, P., Bar-Sagi, D., Margolis, B., Schlessinger, J. (May 1993) Guanine-Nucleotide-Releasing Factor Hsos1 Binds to Grb2 and Links Receptor Tyrosine Kinases to Ras Signaling. Nature, 363 (6424). pp. 85-88. ISSN 0028-0836
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 Grb2/hSos1 complex couples activated EGF receptor to Ras signalling.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | GROWTH-FACTOR VULVAR INDUCTION PC12 CELLS DIFFERENTIATION REQUIREMENT P21RAS.GTP SEVENLESS PATHWAY GENE |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > epidermal growth factor 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: | 6 May 1993 |
| Date Deposited: | 12 Apr 2016 14:56 |
| Last Modified: | 12 Apr 2016 14:56 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/32573 |
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