Our laboratory has been conducting biochemical investigations on G protein mediated signal transduction pathways. The main theme is to understand the regulatory mechanism of activation of Rho family GTPases (Rho, Rac, Cdc42) by heterotrimeric G proteins. Rho family GTPases are involved in a variety of cellular functions mainly by controlling the organization of actin cytoskeleton. We have recently demonstrated that G 12 and G 13, whose effectors were previously unknown, interact with and regulate the activity of a novel Rho specific GEF (guanine nucleotide exchange factor), p115RhoGEF. This result was the first demonstration of the biochemical link between Rho family monomeric GTPases and heterotrimeric G proteins. We will characterize the regulation of p115RhoGEF by G 12/G 13 in detail by reconstituting purified components and also using cultured cell lines. The involvement of this signaling pathway in cellular functions such as neurite extension, angiogenesis, chemotaxis, or cell-cell adhesion will be pursued in future. We are also trying to find new effectors for G protein signaling pathways. We have recently identified a brain specific effector candidate GRIN1 for G {alpha}. G {alpha} is an extremely abundant protein in the brain but its physiological function is unknown. Both G {alpha} and GRIN1 are highly enriched at growth cone of neuron.  In addition, we demonstrated that activation of G {alpha}-GRIN1 pathway stimulates neurite formation in cultured cells. We will further investigate the physiological significance of this signaling pathway in brain function.

Lab Members