INSULIN AND INTERLEUKIN-1 DIFFERENTIALLY REGULATE PP63, AN ACUTE-PHASE PHOSPHOPROTEIN IN HEPATOMA-CELL LINE

We have reported previously that the phosphoprotein pp63, an acute pha se protein, which has been recently identified as the rat fetuin, was capable of blocking the mitogenic effect of insulin on the rat Fao hep atoma cell line, without affecting metabolic effects of the hormone. O nly the phosphorylated form of the protein has been shown to exhibit b oth anti-tyrosine kinase and growth inhibitory properties. In this stu dy, we used the FTO-2B rat hepatoma cell line to analyze the mechanism s involved in the control of synthesis and/or phosphorylation of pp63. For this purpose, we investigated the action of effectors known to mo dulate hepatic functions, such as cytokines (interleukin (IL)-1 beta a nd IL-6), which regulate the production of acute phase proteins, and i nsulin, which elicits profound effects on hepatocyte metabolism. Here, we demonstrate that IL-1 beta diminished markedly the pp63 production by affecting its m;RNA transcription and that the cytokine was able t o modify the N-glycosylation process of the protein. In contrast, insu lin did not affect the biosynthesis of pp63 but dramatically decreased its extent of phosphorylation.