Akhoundi C, Amiot M, Auberger P, Le Cam A, Rossi B
INSERM U-364 Faculté de Médecine, Nice, France.
J Biol Chem. 1994 Jun 3;269(22):15925-30.
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.
我们之前报道过，磷蛋白pp63是一种急性期蛋白，最近被鉴定为大鼠胎球蛋白，它能够阻断胰岛素对大鼠Fao肝癌细胞系的促有丝分裂作用，而不影响该激素的代谢作用。只有该蛋白的磷酸化形式显示出抗酪氨酸激酶和生长抑制特性。在本研究中，我们使用FTO-2B大鼠肝癌细胞系来分析参与pp63合成和/或磷酸化调控的机制。为此，我们研究了已知可调节肝功能的效应物的作用，如调节急性期蛋白产生的细胞因子（白细胞介素（IL）-1β和IL-6），以及对肝细胞代谢有深远影响的胰岛素。在此，我们证明IL-1β通过影响其mRNA转录显著减少了pp63的产生，并且该细胞因子能够改变该蛋白的N-糖基化过程。相比之下，胰岛素不影响pp63的生物合成，但显著降低了其磷酸化程度。
