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 o f EGF-stimulated hepatocytes was significantly and transiently increas ed at the G(1)/S transition, being about 2.5-fold, while that in non-s timulated hepatocytes showed almost no change. On the other hand, non- nuclear PP1 activity was gradually increased until the G(1)/S transiti on, but the activity showed no difference between EGF-stimulated and n on-stimulated hepatocytes. Under growth-inhibited conditions in the pr esence of TGF beta 1, the increase in nuclear PP1 activity was complet ely 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 inv olvement 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 conditi ons. Mechanism(s) of growth-associated alterations in nuclear PP1 acti vity is discussed.