CELL TRANSFORMATION BY INSULIN AND IGF1 RECEPTORS

胰岛素和 IGF1 受体的细胞转化

• 批准号: 2837652
• 负责人: LU-HAI WANG
• 金额: $ 27.89万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-06-01 至 2002-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2837652
• 关键词: G protein; biological signal transduction; cell growth regulation; cell line; cell transformation; contact inhibition; growth factor receptors; insulin receptor; insulinlike growth factor; mutant; oncoproteins; phosphatidylinositol 3 kinase; transfection; yeast two hybrid system

The goal of the proposed study is to elucidate signal transduction pathways that are important in mediating the oncogenic insulin and insulin-like growth factor I receptors (IR and IGFR)-induced cell growth and transformation, and to explore novel signaling molecules for these receptors. IR and IGFR are two receptor tyrosine kinases which play important roles in regulating cellular metabolic activities, growth and differentiation. The focus will be on identifying the specific Rho/Rac/Cdc42-mediated signaling pathways and molecules involved in regulating distinct cell transforming properties. The major approach will employ loss-of-function mutants of the oncogenic IR and IGFR, as well as various activated and dominant inhibitory mutants of the signaling molecules of Rho/Rac/Cdc42, IRS-1 and P13 kinase to dissect their signal transduction pathways important for cell growth and transformation. The specific aims are: 1. To investigate the effect of oncogenic IR and IGFR and their loss-of-function mutants on Rho/Rac/Cdc42-mediated signaling functions. 2. To elucidate the Rho/Rac/Cdc42-mediated signaling pathways involved in regulating the oncogenic IR and IGFR-induced cell growth and transformation. 3. To explore the role of IRS-1 and P13 kinase in the oncogenic IR and IGFR- induced cell growth and transformation. 4. To explore the role of an IGFR-interacting G beta-related protein, named IGIP, in IGFR signaling functions.

拟议的研究的目的是阐明信号转导 对于介导致癌胰岛素和 胰岛素样生长因子I受体（IR和IGFR）诱导的细胞生长 和转化，并探索这些新型信号分子 受体。 IR和IGFR是两个受体酪氨酸激酶 在调节细胞代谢活性，生长和 分化。 重点将是确定特定 RHO/RAC/CDC42介导的信号通路和分子参与 调节不同的细胞转换特性。 主要方法 将采用致癌性IR和IGFR的功能丧失突变体，作为 以及各种激活和显性抑制突变体 RHO/RAC/CDC42，IRS-1和P13激酶的信号分子剖析 它们对细胞生长和 转型。 具体目的是：1。研究 致癌IR和IGFR及其在功能丧失上突变体 RHO/RAC/CDC42介导的信号传导函数。 2。阐明 RHO/RAC/CDC42介导的信号通路涉及调节 致癌IR和IGFR诱导的细胞生长和转化。 3 探索IRS-1和P13激酶在致癌IR和IGFR-的作用 诱导细胞生长和转化。 4。探索一个 IGFR信号传导中的IGFR相互作用Gβ相关蛋白，称为IGIP 功能。