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 phase protein, which has been recently identified as the rat fetuin, was capable of blocking the mitogenic effect of insulin on the rat Fao hepatoma cell line, without affecting metabolic effects of the hormone. Only the phosphorylated form of the protein has been shown to exhibit both anti-tyrosine kinase and growth inhibitory properties. In this study, we used the FTO-2B rat hepatoma cell line to analyze the mechanisms involved in the control of synthesis and/or phosphorylation of pp63. For this purpose, we investigated the action of effectors known to modulate hepatic functions, such as cytokines (interleukin (IL)-1 beta and IL-6), which regulate the production of acute phase proteins, and insulin, which elicits profound effects on hepatocyte metabolism. Here, we demonstrate that IL-1 beta diminished markedly the pp63 production by affecting its mRNA transcription and that the cytokine was able to modify the N-glycosylation process of the protein. In contrast, insulin did not affect the biosynthesis of pp63 but dramatically decreased its extent of phosphorylation.
Akhoundi
C
C
INSERM U-364 Faculté de Médecine, Nice, France.
Amiot
M
M
Auberger
P
P
Le Cam
A
A
Rossi
B
B
D000209:Acute-Phase Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D015972:Gene Expression Regulation, Neoplastic; D006031:Glycosylation; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental; D008297:Male; D010750:Phosphoproteins / Q000096:biosynthesis* / Q000302:isolation & purification; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D000509:alpha-Fetoproteins / Q000096:biosynthesis* / Q000302:isolation & purification
D000209:Acute-Phase Proteins; D007328:Insulin; D007375:Interleukin-1; D015850:Interleukin-6; D010750:Phosphoproteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; C047026:acute-phase phosphoprotein pp63; D000509:alpha-Fetoproteins; D003907:Dexamethasone