GROWTH factors such as platelet-derived growth factor and epidermal growth factor (EGF) bind to and activate cell-surface receptors with intrinsic tyrosine kinase activities1. Receptor activation elicits multiple physiological changes in target cells, including alterations in gene expression2–4. Receptor tyrosine kinase signalling involves recruitment of proteins into a signalling complex through interactions between receptor autophosphorylation sites and the src-homology region-2 (SH2) domains on these signalling proteins5–9. Diverse signals can subsequently be generated, depending on the specific receptor and cell type2,10. How such signals are transmitted to the nucleus is poorly understood, but because the transcriptional activation of many genes by growth factors occurs in the absence of new protein synthesis4, one or more signals emanating from growth factor receptors must directly affect transcription factors. We report here the activation by EGF of a DNA-binding protein in a cell-free system where activation of DNA binding requires ligand, receptor, ATP and phosphotyrosine–SH2 interactions.
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Sadowski, H., Gilman, M. Cell-free activation of a DNA-binding protein by epidermal growth factor. Nature 362, 79–83 (1993). https://doi.org/10.1038/362079a0
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