CELL TRANSFORMATION BY INSULIN AND IGF1 RECEPTORS

这项研究的目的是阐明信号转导 在介导致癌胰岛素中起重要作用的途径， 胰岛素样生长因子I受体（IR和IGFR）诱导的细胞生长 和转化，并探索新的信号分子， 受体。 IR和IGFR是两种受体酪氨酸激酶， 在调节细胞代谢活动、生长和 分化 重点将是确定具体的 Rho/Rac/Cdc 42介导的信号通路和参与的分子 调节不同的细胞转化特性。 主要方法 将使用致癌IR和IGFR的功能丧失突变体， 以及各种激活和显性抑制突变体的 Rho/Rac/Cdc 42、IRS-1和P13激酶的信号分子，以解剖 它们的信号转导途径对细胞生长和 转型 具体目标是：1.探讨了影响 致癌IR和IGFR及其功能丧失突变体， Rho/Rac/Cdc 42介导的信号传导功能。 2.阐明本 Rho/Rac/Cdc 42介导的信号通路参与调节细胞凋亡。 致癌IR和IGFR诱导的细胞生长和转化。 3.到 探讨IRS-1和P13激酶在癌基因IR和IGFR中的作用。 诱导细胞生长和转化。 4.为了探索一个 IGFR相互作用的G β相关蛋白，命名为IGIP，在IGFR信号传导中 功能协调发展的

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.