Involvement of polyamines in retinoblastoma protein phosphorylation.
Hepatocyte growth factor (HGF) increased both levels of phosphorylated and non-phosphorylated forms of retinoblastoma protein (RB) in primary cultured rat hepatocytes. Combined treatment of HGF and a specific inhibitor of ornithine decarboxylase (ODC), alpha-difluoromethylornithine (DFMO), reduced the levels of hyper-phosphorylated and hypo-phosphorylated forms of RB and increased the levels of the non-phosphorylated form, compared to HGF alone, but did not affect the total level of RB. Polyamines added exogenously overcame the effects of DFMO; they increased hyper- and hypo-phosphorylated forms and decreased non-phosphorylated RB. TGF-beta1 inhibited the increases in ODC activity, RB phosphorylation, and DNA synthesis induced by HGF. However, polyamines added exogenously could not overcome the inhibition by RB phosphorylation and DNA synthesis by TGF-beta1. These results suggest that polyamines are involved in the phosphorylation of RB, but the inhibition of polyamine biosynthesis by TGF-beta1 did not result in the inhibition of RB phosphorylation and DNA synthesis.
Department of Biochemistry, Osaka City University Medical School, Osaka, Asahimachi, Abeno-ku, 545-8585, Japan.
T
T
Omura
Y
Y
Yano
T
T
Hasuma
H
H
Kinoshita
I
I
Matsui-Yuasa
S
S
Otani
D000818:Animals; D002478:Cells, Cultured; D000518:Eflornithine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009955:Ornithine Decarboxylase / Q000378:metabolism* / Q000494:pharmacology; D065108:Ornithine Decarboxylase Inhibitors; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D016160:Retinoblastoma Protein / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D004791:Enzyme Inhibitors; D065108:Ornithine Decarboxylase Inhibitors; D016160:Retinoblastoma Protein; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor; D009955:Ornithine Decarboxylase; D000518:Eflornithine