Cell-free activation of a DNA-binding protein by epidermal growth factor.
Growth factors such as platelet-derived growth factor and epidermal growth factor (EGF) bind to and activate cell-surface receptors with intrinsic tyrosine kinase activities. Receptor activation elicits multiple physiological changes in target cells, including alterations in gene expression. 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 proteins. Diverse signals can subsequently be generated, depending on the specific receptor and cell type. 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 synthesis, 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.
Sadowski
H B
HB
Cold Spring Harbor Laboratory, New York 11724-2206.
Gilman
M Z
MZ
D016475:3T3 Cells; D000818:Animals; D002458:Cell Fractionation / Q000379:methods; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002474:Cell-Free System; D003600:Cytosol / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D004229:Dithiothreitol / Q000494:pharmacology; D004331:Drosophila melanogaster; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D016762:Genes, fos; D006801:Humans; D051379:Mice; D019000:Phosphotyrosine; D015398:Signal Transduction; D014158:Transcription, Genetic; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014461:Ultracentrifugation
D004268:DNA-Binding Proteins; D019000:Phosphotyrosine; D014443:Tyrosine; D004815:Epidermal Growth Factor; D004229:Dithiothreitol