Hazel T G, Misra R, Davis I J, Greenberg M E, Lau L F
Department of Genetics, University of Illinois College of Medicine, Chicago 60612.
Mol Cell Biol. 1991 Jun;11(6):3239-46. doi: 10.1128/mcb.11.6.3239-3246.1991.
The rat pheochromocytoma cell line PC12 can be induced by growth factors to undergo proliferation and neuronal differentiation. These cells also have excitable membranes that can be depolarized by neurotransmitters or elevated levels of extracellular KCl. Treatment of PC12 cells with growth factors or membrane-depolarizing agents rapidly activates the expression of specific genes whose products are thought to mediate the subsequent biological responses. One such gene, nur77, is a member of the steroid and thyroid hormone receptor gene superfamily. We have identified the Nur77 protein and shown that it is synthesized rapidly and transiently in PC12 cells following stimulation, has a short half-life of 30 to 40 min, and is located in both the nucleus and the cytoplasm. Nur77 is posttranslationally modified, primarily by phosphorylation on serine residues. Phosphopeptide analysis reveals that Nur77 is modified differently upon membrane depolarization than after treatment with growth factors. We hypothesize that the activity of Nur77 is regulated by both differential gene expression and posttranslational modification and that these modes of regulation contribute to distinct downstream responses specific to membrane depolarization and growth factor treatment.
大鼠嗜铬细胞瘤细胞系PC12可被生长因子诱导进行增殖和神经元分化。这些细胞还具有可兴奋膜，可被神经递质或细胞外氯化钾水平升高 depolarized。用生长因子或膜去极化剂处理PC12细胞可迅速激活特定基因的表达，其产物被认为介导随后的生物学反应。其中一个这样的基因，nur77，是类固醇和甲状腺激素受体基因超家族的成员。我们已经鉴定出Nur77蛋白，并表明它在刺激后在PC12细胞中迅速且短暂地合成，半衰期短，为30至40分钟，并且位于细胞核和细胞质中。Nur77在翻译后被修饰，主要是丝氨酸残基的磷酸化。磷酸肽分析表明，膜去极化时Nur77的修饰与生长因子处理后的修饰不同。我们假设Nur77的活性受差异基因表达和翻译后修饰的调节，并且这些调节模式有助于膜去极化和生长因子处理特有的不同下游反应。 （原文中“depolarized”可能有误，推测应该是“去极化”之类的专业术语，可根据实际情况修正）
