BASIS FOR TRANSFORMATION BY FUJINAMI SARCOMA VIRUS

富士肉瘤病毒转化的基础

基本信息

批准号：
3458702
负责人：
DAVID A FOSTER
金额：
$ 11.66万
依托单位：
HUNTER COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-08-25 至 1994-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3458702
关键词：
Aves Retroviridae Retroviridae disease biological signal transduction enzyme inhibitors gene expression genetic transcription laboratory rat neoplasm /cancer pharmacology oncogenes phospholipase A2 phospholipase C protein kinase C protein tyrosine kinase temperature sensitive mutant viral carcinogenesis virus genetics

项目摘要

The objective of the proposed research is to understand how protein- tyrosine kinase oncongenes transform cells. The major emphasis is on the fps gene of Fujinami sarcoma virus. We will characterize signal transduction pathways used by v-fps to transform cells. We have developed a pharmaco-genetic approach for identifying signal transduction intermediates used by the v-fps gene product to transduce signals to the nucleus. Elevating the protein-tyrosine kinase activity of a temperature-sensitive derivative of v-fps, leads to the rapid transcriptional activation of the recently characterized 9E3 gene whose expression correlates with transformation (Sugano et al., Cell 49, 1321,-328, 1987). Drugs that interfere with known signal transduction intermediates are used to block the induction of 9E3 gene expression. In this way, we can determine if specific signal transduction intermediates are required for v-fps to induce expression of the transformation-related 9E3 gene. The pharmacological approach involves the generation of detailed drug- sensitivity profiles (DSPs) for inhibitors of signal transduction that are diagnostic for the involvement of specific signal transduction intermediates. Using several protein kinase C requirement. In addition, we have preliminary data suggesting a requirement for protein kinase C, a cholera toxin-sensitive G-protein, phospholipase C, and phospholipase A2 in the v-fps induction of 9E3 gene expression. Experiments proposed here will directly demonstrate the involvement of these implicated signal transduction intermediates in transformation by v-fps. The data to be generated from these studies may provide new targets and strategies for cancer chemotherapy in cases where protein-tyrosine kinase activity has been implicated.

拟议研究的目的是了解蛋白质如何酪氨酸激酶癌基因转化细胞。主要强调的是富士并肉瘤病毒的 fps 基因。我们将表征信号 v-fps 用于转化细胞的转导途径。我们开发了一个鉴定信号转导中间体的药物遗传学方法由 v-fps 基因产物用来将信号转导至细胞核。提高温度敏感蛋白酪氨酸激酶活性 v-fps 的衍生物，导致快速转录激活最近鉴定了 9E3 基因，其表达与转化（Sugano 等人，Cell 49, 1321,-328, 1987）。药物干扰已知信号转导的中间体用于阻断 9E3基因表达的诱导。这样我们就可以判断是否 v-fps 需要特定的信号转导中间体来诱导转化相关9E3基因的表达。药理学方法涉及生成详细的药物- 信号转导抑制剂的敏感性概况 (DSP) 特定信号转导参与的诊断中间体。使用几种蛋白激酶C的要求。此外，我们初步数据表明需要蛋白激酶 C，霍乱毒素敏感 G 蛋白、磷脂酶 C 和磷脂酶 A2 9E3基因表达的v-fps诱导。这里提出的实验将直接证明这些隐含信号的参与 v-fps 转化中的转导中间体。待数据这些研究产生的结果可能会提供新的目标和策略蛋白质酪氨酸激酶活性降低的情况下的癌症化疗受到牵连。