Constitutive phosphorylation of the epidermal growth factor receptor blocks mitogenic signal transduction.
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.
Bowen
S
S
Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester 01605.
Stanley
K
K
Selva
E
E
Davis
R J
RJ
D000818:Animals; D001345:Autoradiography; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation; D066246:ErbB Receptors / Q000378:metabolism*; D008934:Mitogens; D009154:Mutation; D010766:Phosphorylation; D010957:Plasmids; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013912:Threonine / Q000235:genetics; D014443:Tyrosine / Q000378:metabolism
D008934:Mitogens; D013912:Threonine; D014443:Tyrosine; D066246:ErbB Receptors; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate