Cell-cycle-dependent modulation of EGF-receptor-mediated signaling

In A431 cells synchronized by treatment with thymidine, the level of EGF-stimulated tyrosine protein kinase activity in cells in S and G₂/M phases was reduced ˜40% relative to that seen in cells in G₁. This decrease in receptor tyrosine protein kinase activity did not correlate with a decrease in cell surface EGF receptor expression, indicating that the reduced activity could not be attributed to receptor loss. EGF-stimulated PI 3-kinase activity was also reduced by ˜60% during S phase as compared to G₁ phase. The change was not due to decreased PI 3-kinase expression since Western blot analyses indicated that cellular p85 levels remained constant throughout the cell These data suggest that the ability of EGF to stimulate biological responses varies during implicate cell-cycle-dependent processes in the regulation of EGF-receptor-mediated signaling.