AVIAN ERYTHROLEUKEMIA AND C-ERB-B ACTIVATION

禽红白血病和 C-ERB-B 激活

• 批准号: 2089754
• 负责人: Hsing-Jien Kung
• 金额: $ 25.88万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-01-01 至 1995-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2089754
• 关键词: RNA splicing; Retroviridae disease; alpharetrovirus; avian leukosis /sarcoma; biological signal transduction; cell growth regulation; chickens; epidermal growth factor; erythroid stem cell; erythroleukemia; fibroblast growth factor; gene expression; genetic mapping; genetic promoter element; genetic transcription; growth factor receptors; host organism interaction; intracellular; leukocyte activation /transformation; ligands; molecular cloning; monocyte; myeloid stem cell; oncogenes; protooncogene; provirus; site directed mutagenesis; transcription factor; transfection; transforming growth factors; viral leukemogenesis; virus DNA; virus envelope; virus genetics; western blottings

Naturally occurring chicken erythroblastosis is induced by non-acute retroviruses through proviral insertion-activation of the c-erbB protooncogene, which encodes epidermal growth factor receptor. The resulting oncogenic erbB molecule is a truncated receptor with deregulated tyrosine kinase activity. This system has provided a fascinating model for studying not only the mechanisms of retroviral insertional mutagenesis and retroviral transductivity but also the growth signaling by a receptor-oncogene. Substantial progress has been made in the past granting period to understand the basis of these issues. One of the striking findings is related to the tissue-specific transformation by the truncated erbB/EGFR molecule. Modulation of the structure of the receptor either in the regulatory or catalytic domain by various mutations changes the oncogenic spectrum of the viruses. The findings suggest the existence of tissue-specific interactions between the receptor and the cellular machinery. Using retrovirus as a genetic tool and other molecular biological approaches, we wish to exploit the uniqueness of the chicken c-erbB system to understand (1) the tissue-specific transformation and intracellular signaling by c-erbB and (2) the ligand-receptor interaction and extracellular signaling by c-erbB.

自然发生的鸡成红细胞增多症是由非急性 逆转录病毒通过前病毒插入激活c-erbB 原癌基因，编码表皮生长因子受体。 的 产生的致癌erbB分子是截短的受体， 酪氨酸激酶活性失调。 该系统提供了 不仅研究逆转录病毒的机制， 插入诱变和逆转录病毒转导，而且生长 由受体癌基因发出信号。 取得实质性进展 过去的授予期，以了解这些问题的基础。 之一 这些惊人的发现与组织特异性转化有关， 截短的erbB/EGFR分子。 结构的调制 受体的调节或催化结构域，通过各种 突变改变了病毒的致癌谱。 这些发现 提示存在组织特异性相互作用， 受体和细胞机制。 利用逆转录病毒作为遗传工具 和其他分子生物学方法，我们希望利用 鸡c-erbB系统的独特性，以了解（1） c-erbB的组织特异性转化和细胞内信号传导， (2)配体-受体相互作用和细胞外信号传导， c-erbB。