TRANSFORMING GENES OF AVIAN SARCOMA VIRUSES

这项研究的目的是阐明和识别信号 在介导恶性细胞增殖中起重要作用的转导途径 致癌受体蛋白酪氨酸激酶（RPTK）Ros 它最初是作为一种禽肉瘤病毒的致癌基因被发现的 称为UR 2。Ros的PTK结构域与Ros的PTK结构域具有高度同源性， 胰岛素和胰岛素样生长因子I受体（IR和IGFR）。然而，在这方面， ROS的生理功能似乎与那些 IR和IGFR。这项研究的重点将是确定具体的 不同细胞所需的信号通路和分子 Ros的转换功能主要的方法是使用损失- Ros的功能突变体以及各种激活和显性 信号分子的抑制性突变体来分解信号 Ros的转导途径。 具体目标是： L.建立表达突变型Ros的哺乳动物细胞系， 表征其生物学和生物化学特性。 2.为了阐明Rho/Rac 1/Cdc 42介导的信号通路在细胞凋亡中的作用， 玫瑰诱导的细胞生长和转化。 3.目的探讨IRS-1和PI 3激酶在玫瑰红诱导细胞生长中的作用 和转变。 4.为了探讨细胞骨架蛋白介导的信号转导在Ros-1中的作用， 诱导细胞生长和转化。 5.评估IGF-I受体在ROS诱导的细胞生长中的作用， 转型

The goal of the proposed study is to elucidate and identify the signal transduction pathways that are important in mediating malignant cell transformation of the oncogenic receptor protein tyrosine kinase (RPTK) Ros which was originally discovered as the oncogene of an avian sarcoma virus called UR2. The PTK domain of Ros shares high homology with those of insulin and insulin-like growth factor I receptors (IR and IGFR). However, the physiological function of Ros appears to be rather different than those of IR and IGFR. The focus of this study will be to identify specific signaling pathways and molecules required for the distinct cell transforming functions of Ros. The major approach will employ loss-of- function mutants of Ros as well as various activated and dominant inhibitory mutants of signaling molecules to dissect the signal transduction pathways of Ros. The specific aims are: l. To establish mutant Ros expressing mammalian cell lines and to characterize their biological and biochemical properties. 2. To elucidate the role ofRho/Rac1/Cdc42-mediated signaling pathways in Ros-induced cell growth and transformation. 3. To explore the role of IRS-1 and PI3 kinase in Ros-induced cell growth and transformation. 4. To inquire the role of cytoskeletal protein-mediated signaling in Ros- induced cell growth and transformation. 5. To assess the role of IGF-I receptor in Ros-induced cell growth and transformation.