MECHANISM OF ACTION OF TYPE BETA TRANSFORMING GROWTH FACTOR

该项目的目的是确定该类型的作用机制 β-转化生长因子在体外和体外培养中的作用 活体动物实验和确定多肽的关联性 在不同物种中，在功能上等同于转化生长因子-β。从机械上讲， 将特别强调对切换的识别 活跃在控制细胞双功能反应中的机制 转化生长因子-β。到目前为止，已经发现了三种不同类别的分子 影响细胞对转化生长因子-β的反应；包括1)其他 多肽生长因子，如转化生长因子-α，表皮生长因子，和 血小板衍生生长因子；2)维甲酸和其他低分子量 3)癌基因及其多肽产物。这其中的每一个 已知物质的种类会影响基因的表达。这些工具将 用于评估转化生长因子-β功能的本项目将包括具体 生物测定、受体测定、免疫测定和转化生长因子-β信使测定 核糖核酸。机械学研究的目标是两个层面：在整个动物和 在原代细胞和已建立的培养细胞系中均有表达。要确定 不同物种TFG-β的亲缘关系及经典基因克隆 将使用方法学来鉴定和测序互补DNA 在猪和鸡中编码转化生长因子-β的序列。

The purpose of the project is to determine the mechanism of action of type beta transforming growth factor (TGF) both in cell culture in vitro and in animal studies in vivo and to determine the relatedness of peptides functionally equivalent to TGF-beta in different species. Mechanistically, particular emphasis will be placed on identification of the switching mechanisms active in control of the bifunctional responses of cells to TGF-beta. Thus far, three different classes of molecules have been found to influence the response of cells to TGF-beta; these include 1) other polypeptide growth factors such as TGF-alpha, epidermal growth factor, and platelet-derived growth factor; 2) retinoids and other low-molecular weight effectors; and 3) oncogenes and their polypeptide products. Each of these classes of substances is known to affect gene expression. Tools that will be used to assess TGF-beta function in this project will include specific bioassays, receptor assays, immunoassays, and assays for TGF-beta messenger RNA. Mechanistic studies are aimed at two levels: in the whole animal and in both primary cells and established cell lines in culture. To determine the relatedness of TFG-betas from different species, classical gene-cloning methodology will be used to identify and sequence complementary DNA sequences coding for TGF-beta in both the pig and the chicken.