TGF-BETA-1 SUPPRESSES EGF-INDUCED INCREASE IN NUCLEAR TYPE-1 PROTEIN PHOSPHATASE-ACTIVITY AT THE G(1)/S TRANSITION OF HEPATOCYTE PROLIFERATION

Nuclear type 1 protein phosphatase (PP1) activity in primary culture of EGF-stimulated hepatocytes was significantly and transiently increased at the G(1)/S transition, being about 2.5-fold, while that in non-stimulated hepatocytes showed almost no change. On the other hand, non-nuclear PP1 activity was gradually increased until the G(1)/S transition, but the activity showed no difference between EGF-stimulated and non-stimulated hepatocytes. Under growth-inhibited conditions in the presence of TGF beta 1, the increase in nuclear PP1 activity was completely suppressed, whereas non-nuclear PP1 activity was little affected. Such close correlation between nuclear PP1 activity and growth factor-induced positive or negative growth signaling strongly suggests an involvement of PP1 in progression from G(1) to S phase of hepatocytes. On Western immunoblotting using antisera for PP1 alpha, PP1 gamma 1, and PP1 delta, no isoform showed any change in amount under these conditions. Mechanism(s) of growth-associated alterations in nuclear PP1 activity is discussed.