CELL TRANSFORMATION BY INSULIN AND IGF1 RECEPTORS

这项拟议研究的目标是阐明信号转导 在调节致癌胰岛素和 胰岛素样生长因子I受体(IR和IGFR)诱导的细胞生长 和转化，并探索这些新的信号分子 感受器。IR和IGFR是两种发挥作用的受体酪氨酸激酶 在调节细胞代谢活动、生长和 差异化。重点将放在确定特定的 Rho/Rac/Cdc42介导的信号转导途径和分子参与 调节不同的细胞转化特性。主要方法 将使用致癌IR和IGFR的功能缺失突变体，AS 以及各种激活的和显性抑制的突变体 Rho/Rac/CDc42、IRS-1和P13激酶信号分子的剖析 它们的信号转导通路对细胞生长和 转型。具体目的是：1.调查 癌基因IR和IGFR及其功能缺失突变体 Rho/RAC/CDC42介导的信号转导功能。2.澄清 Rho/Rac/CDC42介导的信号通路参与调控 致癌IR和IGFR诱导的细胞生长和转化。3.至 探讨IRS-1和P13激酶在致癌IR和IGFR-1中的作用 诱导细胞生长和转化。4.探索企业的角色 IGFR信号通路中与IGFR相互作用的Gβ相关蛋白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.