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 primar y cultured rat hepatocytes, Combined treatment of HGF and a specific i nhibitor of ornithine decarboxylase (ODC), alpha-difluoromethylornithi ne (DFMO), reduced the levels of hyper-phosphorylated and hypo-phospho rylated forms of RE and increased the levels of the nonphosphorylated form, compared to HGF alone, but did not affect the total level of RE. Polyamines added exogenously overcame the effects of DFMO; they incre ased hyper- and hypo-phosphorylated forms and decreased non-phosphoryl ated RE. TGF-beta 1 inhibited the increases in ODC activity, RE phosph orylation, and DNA synthesis induced by HGF. However, polyamines added exogenously could not overcome the inhibition by RE phosphorylation a nd DNA synthesis by TGF-beta 1. These results suggest that polyamines are involved in the phosphorylation of RE, but the inhibition of polya mine biosynthesis by TGF-beta 1 did not result in the inhibition of RE phosphorylation and DNA synthesis. (C) 1998 Academic Press.