Association of Sos Ras exchange protein with Grb2 is implicated in tyrosine kinase signal transduction and transformation

• Published in: Nature (London) 1993-05, Vol.363 (6424), p.45-51
• Main Authors: Egan, Sean E, Giddings, Barton W, Brooks, Mary W, Buday, László, Sizeland, Andrew M, Weinberg, Robert A
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Caenorhabditis elegans; Cell Differentiation; Cell physiology; Cells, Cultured; Cellular biology; Cloning, Molecular; DNA, Single-Stranded; Drosophila; Drosophila melanogaster; Fundamental and applied biological sciences. Psychology; GRB2 Adaptor Protein; Humanities and Social Sciences; Humans; Membrane Proteins - metabolism; Mice; Molecular and cellular biology; Molecular Sequence Data; multidisciplinary; Protein Binding; Protein-Tyrosine Kinases - metabolism; Proteins; Proteins - metabolism; Proto-Oncogene Proteins p21(ras) - metabolism; Rats; Receptor, Epidermal Growth Factor - metabolism; Science; Science (multidisciplinary); Signal Transduction; Son of Sevenless Proteins
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/363045a0

The proteins Grb2–Sem-5, Shc and Sos have been implicated in the signalling pathway from tyrosine kinase receptors to Ras. Grb2–Sem-5 binds directly to murine Sos1, a Ras exchange factor, through two SH3 domains. Sos is also associated with ligand-activated tyrosine kinase receptors which bind Grb2–Sem-5, and with the Grb2–Sem-5 binding protein, Shc. Ectopic expression of Drosophila Sos stimulates morphological transformation of rodent fibroblasts. These data define a pathway by which tyrosine kinases act through Ras to control cell growth and differentiation.