Abstract
The function of epidermal growth factor receptor (EGFR) was found to be negatively regulated in M phase in which it showed less phosphotyrosine content and reduced intrinsic kinase activity accompanied by retarded electrophoretic mobility owing to total hyperphosphorylation. Ligand-induced autophosphorylation and downstream signaling of EGFR were tightly suppressed in M phase due to a decrease in ligand binding affinity and the inability of epidermal growth factor (EGF) to induce receptor dimerization. There was no change in the number of surface-exposed EGF receptors between G0/G1 and M phases of the cell cycle. Hyperphosphorylation (due to serine and/or threonine phosphorylation) correlates with the unresponsiveness of cells to EGF-mediated stimulation of tyrosine phosphorylation in cells that express the normal or basal level of EGFR. This M phase-specific negative regulation was overcome by overexpression of EGFR, which was responsive to ligand throughout the cell cycle and revealed ligand-induced signaling in the M phase. These findings indicate that EGFR does not respond to ligand stimulation in M phase and suggest that a negative regulation of ligand- receptor interactions in M phase may control the normal function of receptor tyrosine kinase and that receptor overexpression will disrupt this cell cycle-dependent regulation of receptor tyrosine kinases.
Original language | English (US) |
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Pages (from-to) | 18656-18665 |
Number of pages | 10 |
Journal | Journal of Biological Chemistry |
Volume | 272 |
Issue number | 30 |
DOIs | |
State | Published - 1997 |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology