Mutational removal of the major site of serine phosphorylation of the epidermal growth factor receptor causes potentiation of signal transduction: role of receptor down-regulation.
The major site of epidermal growth factor receptor (EGF-R) serine phosphorylation is located within the COOH-terminal domain of the receptor at Ser1046/7. We have previously demonstrated that this phosphorylation site accounts for the acute desensitization of the EGF-R observed in EGF-treated cells. Here we show that the mutational removal of this negative regulatory phosphorylation site causes potentiation of signal transduction by the EGF-R. This potentiation can be accounted for in part by a block in the EGF-stimulated down-regulation of the EGF-R. These data indicate that the SER1046/7 phosphorylation site may have a regulatory role during long term incubation of cells with mitogenic concentrations of EGF.
Theroux
S J
SJ
Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biology, University of Massachusetts Medical School, Worcester 01605.
Stanley
K
K
Campbell
D A
DA
Davis
R J
RJ
D000494:Allosteric Regulation; D000818:Animals; D016466:CHO Cells; D002455:Cell Division; D006224:Cricetinae; D015536:Down-Regulation; D016296:Mutagenesis; D010766:Phosphorylation; D010768:Phosphoserine; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
D010768:Phosphoserine