All cells and organisms detect chemical and physical changes in their environment via cell surface receptors. Information collected by these receptors regarding the concentration of hormones, growth factors or sensory stimuli is transduced into intracellular changes in regulatory molecules that control cell growth and differentiated cell function. We have teen studying the GTP-binding protein family. The G-proteins are generally composed of alpha, beta and gamma subunits, and to serve to couple receptors to a variety of changes in intracellular metabolism. Our work has led to the partial characterization of a family of genes that encode the G-proteins. In continuing this work we will determine the extent of diversity in the G-protein gene family in mammals by isolating cDNA clones corresponding to G-protein subunits in various tissues. We will test the hypothesis that there are specialized G-proteins in highly differentiated cells that couple to specific receptor and effectors. We plan to generate variant G-protein cDNAs by in vitro mutagenesis. Gene product expression and overproduction systems will be developed to study the effects of specific modifications in the amino acid sequence of the G- protein subunits on signal transduction activity. The experiments will focus on understanding the structural basis for specificity in the interaction of G-proteins with receptors and effectors and the regulation of G-protein function. In vivo studies will be designed to understand the nature of the interaction between different G-proteins and the intracellular integration of signals. We will also define the mechanisms that control specific G-protein gene expression in differentiated cells.
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