MECHANISM OF ACTION OF TYPE BETA TRANSFORMING GROWTH FACTOR

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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.