CELL TRANSFORMATION BY INSULIN AND IGF1 RECEPTORS

拟议研究的目标是阐明信号转导 介导致癌胰岛素的重要途径 胰岛素样生长因子 I 受体（IR 和 IGFR）诱导的细胞生长 和转化，并探索这些新的信号分子 受体。 IR 和 IGFR 是两种受体酪氨酸激酶，其作用 在调节细胞代谢活动、生长发育等方面发挥着重要作用 差异化。 重点将是确定具体的 Rho/Rac/Cdc42 介导的信号通路和分子参与 调节不同的细胞转化特性。 主要方法 将采用致癌 IR 和 IGFR 的功能丧失突变体，如 以及各种激活和显性抑制突变体 解析 Rho/Rac/Cdc42、IRS-1 和 P13 激酶的信号分子 它们的信号转导途径对细胞生长很重要 转变。 具体目的是： 1. 考察效果 致癌 IR 和 IGFR 及其功能丧失突变体 Rho/Rac/Cdc42 介导的信号传导功能。 2. 阐明 Rho/Rac/Cdc42 介导的信号通路参与调节 致癌 IR 和 IGFR 诱导细胞生长和转化。 3. 至 探讨 IRS-1 和 P13 激酶在致癌 IR 和 IGFR 中的作用 诱导细胞生长和转化。 4. 探索角色 IGFR 信号转导中的 IGFR 相互作用 G β 相关蛋白，称为 IGIP 功能。

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.