TGF beta 1 suppresses EGF-induced increase in nuclear type 1 protein phosphatase activity at the G1/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 G1/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 G1/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 G1 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.
Kakinoki
Y
Y
Section of Biochemistry, Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Mizuno
Y
Y
Takizawa
N
N
Imai
Y
Y
Miyazaki
T
T
Kikuchi
K
K
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division; D002467:Cell Nucleus / Q000201:enzymology*; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D016193:G1 Phase; D015870:Gene Expression; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D016196:S Phase; D013347:Subcellular Fractions / Q000201:enzymology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D007527:Isoenzymes; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D010749:Phosphoprotein Phosphatases