The elevation of cellular phosphatidic acid levels caused by polyomavirus transformation can be disassociated from the activation of phospholipase D.
The elevation of cellular phosphatidic acid levels caused by polyomavirus transformation can be disassociated from the activation of phospholipase D.
复制标题
多瘤病毒转化引起的细胞磷脂酸水平升高与磷脂酶 D 的激活无关。
DOI：
10.1006/viro.1997.8630
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Gorga,FR
中科院分区：
文献类型：
--
作者：
Vasudevan,C;Freund,R;Gorga,FR
Middle T (mT) 是鼠多瘤病毒的癌基因，通过激活多肽生长因子及其受体通常使用的许多信号转导途径引起大鼠成纤维细胞的转化。在这里，我们报告了有关涉及磷脂酶 D (PL-D) 的信号转导途径激活的数据。 PL-D 水解磷脂产生磷脂酸 (PA)，这是一种具有多种生物效应的化合物。通过多种不同方法引入的表达野生型 mT 的细胞的 PA 含量比未转化的对应细胞高约 50%。细胞 PA 含量的增加与表达野生型 mT 的细胞中 PL-D 活性增加约 65% 相关。我们还研究了一些 mT 定点突变体对细胞 PA 水平和 PL-D 活性的影响。不产生 mT (Py808A) 或产生截短的非膜结合 mT (Py1387T) 的突变体具有与对照细胞相似的 PA 水平。表达 mT 322YF 突变体（消除 mT 与磷脂酶 C γ1 的相互作用）的细胞显示 PA 水平和 PL-D 活性均增加，与野生型 mT 相似。消除 mT 与 shc 或与磷脂酰肌醇 3-激酶（分别为 250YS 和 315YF）相互作用的突变体的表达导致 PL-D 活性增加，与野生型 mT 所见的相当。然而，表达这些突变体的细胞的 PA 含量并未升高。这些结果表明 mT 引起细胞 PL-D 的激活，但仅这种激活不足以引起细胞 PA 含量的增加。因此，野生型 mT 必定会影响 PA 代谢中另一个目前未知的步骤。
Middle T (mT), the oncogene of murine polyomavirus, causes transformation of rat fibroblasts by activating a number of signal transducing pathways usually used by polypeptide growth factors and their receptors. Here, we report data regarding the activation of signal transducing pathways involving phospholipase D (PL-D). The hydrolysis of phospholipids by PL-D produces phosphatidic acid (PA), a compound with multiple biological effects. The PA content of cells expressing wild-type mT, introduced via a number of different methods, is approximately 50% higher than their untransformed counterparts. This increase in cellular PA content is associated with an approximately 65% increase in PL-D activity in cells expressing wild-type mT. We have also examined the effects of a number of site-directed mutants of mT, on both cellular PA levels and on PL-D activity. Mutants that do not produce mT (Py808A) or that produce a truncated, nonmembrane bound mT (Py1387T) have PA levels similar to that of control cells. Cells expressing the 322YF mutant of mT (which abolishes interaction of mT with phospholipase C γ1) show increases in both PA levels and PL-D activity that are similar to those seen with wild-type mT. Expression of mutants that abolish the interaction of mT with either shc or with phosphatidylinositol 3-kinase (250YS and 315YF, respectively) cause an increase in PL-D activity comparable to that seen with wild-type mT. However, the PA content of cells expressing these mutants is not elevated. These results suggest that mT causes activation of cellular PL-D, but this activation alone is not sufficient to cause an increase in cellular PA content. Therefore, wild-type mT must affect another, as yet unknown, step in PA metabolism.