Constitutive phosphorylation of the epidermal growth factor receptor blocks mitogenic signal transduction
Howard Hughes Medical Institute, Program in Molecular Medicine
Animals; Autoradiography; Cells, Cultured; Chromatography, High Pressure Liquid; Cricetinae; Cricetulus; Enzyme Activation; *Mitogens; Mutation; Phosphorylation; Plasmids; Protein Kinase C; Receptor, Epidermal Growth Factor; *Signal Transduction; Tetradecanoylphorbol Acetate; Threonine; Tyrosine
Life Sciences | Medicine and Health Sciences
The epidermal growth factor (EGF) receptor is phosphorylated by protein kinase C at Thr654. It has been proposed that the phosphorylation of this site is an important regulatory mechanism for the control of EGF receptor function. However, the physiological significance of the phosphorylation of EGF receptor Thr654 in intact cells is not understood. To address this question, the design of an experimental strategy is required that can be used to distinguish between the pleiotropic effects of kinase C activation and the specific effects of kinase C that are mediated by the phosphorylation of the EGF receptor at Thr654. The approach that we used was to examine the function of EGF receptors that are constitutively phosphorylated at residue 654. It was observed that the constitutive phosphorylation of the EGF receptor blocked mitogenic signal transduction by the receptor. These data are consistent with the hypothesis that the phosphorylation of the EGF receptor at residue 654 in intact cells inhibits EGF-stimulated cellular proliferation.
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Citation: J Biol Chem. 1991 Jan 15;266(2):1162-9.
The Journal of biological chemistry
Bowen, Sharon; Stanley, Krista; Selva, Erica Marie; and Davis, Roger J., "Constitutive phosphorylation of the epidermal growth factor receptor blocks mitogenic signal transduction" (1991). Open Access Articles. 857.