CELL-CYCLE-DEPENDENT MODULATION OF EGF-RECEPTOR-MEDIATED SIGNALING

In A431 cells synchronized by treatment with thymidine, the level of E GF-stimulated tyrosine protein kinase activity in cells in S and G(2)/ M phases was reduced similar to 40% relative to that seen in cells in G(1). This decrease in receptor tyrosine protein kinase activity did n ot correlate with a decrease in cell surface EGF receptor expression,i ndicating that the reduced activity could not be attributed to recepto r loss. EGF-stimulated PI 3-kinase activity was also reduced by simila r to 60% during S phase as compared to G(1) phase. The change was not due to decreased PI 3-kinase expression since Western blot analyses in dicated that cellular p85 levels remained constant throughout the cell cycle. These data suggest that the ability of EGF to stimulate biolog ical responses varies during the cell cycle and implicate cell-cycle-d ependent processes in the regulation of EGF-receptor-mediated signalin g. (C) 1995 Academic Press, Inc.