It has been shown that guanine nucleotide-binding proteins (G(N) proteins) are involved in the regulation of various key biochemical processes in signal transduction. The goal of this research is to elucidate the molecular mechanisms of interaction between the G proteins and their target effector proteins by molecular genetic approaches. We will use two well-established G protein-target systems; (1) the yeast and mammalian ras protein-yeast adenylate cyclase system, and (2) the mammalian Gs protein-mammalian adenylate cyclase system. In the yeast cyclase system our aim will be to analyse the precise mode of interaction between ras proteins and cyclase, and also to define a structural element in cyclase which is responsible for the interaction with ras proteins. The information on the ras-interaction site will be used to search for the mammalian target(s) of ras proteins. In the mammalian cyclase system, our aim will be to analyse the structural basis of interaction of cyclase with Gs protein and to elucidate the generation mechanism of different forms of cyclases by cloning the gene encoding adenylate cyclase. These two studies taken together could give us insight into the common structural basis of the G protein-target interaction which is applicable to other systems as well as insight into the evolutionary pathway of adenylate cyclase which seems to have switched its regulator from ras proteins in yeast to Gs protein in mammals.
| Suzuki, N; Choe, H R; Nishida, Y et al. (1990) Leucine-rich repeats and carboxyl terminus are required for interaction of yeast adenylate cyclase with RAS proteins. Proc Natl Acad Sci U S A 87:8711-5 |
