Our laboratory studies signal transduction pathways that are mediated by heterotrimeric G proteins in the yeast Saccharomyces cerevisiae. In yeast, stress responses and cellular morphology are controlled by extracellular signals that activate multiple pathways mediated by Ras proteins and the G protein a-subunit Gpa2. These two signaling components work in parallel to activate downstream kinases and perhaps function to integrate different signals into an overall growth rate. One interesting aspect of this system is that the Gpa2 a-subunit appears to function either as a monomer or in association with an unconventional bg complex, in contrast to all other G protein a-subunits described thus far.
We have begun characterizing this pathway by identifying the gene for a G protein-coupled receptor that functions upstream of Gpa2. In addition, we have identified two homologous genes that encode novel effectors that act directly downstream of the G protein. These effectors are kelch repeat-containing proteins that appear to transmit a signal from Gpa2 to protein kinase A (PKA). Recent evidence suggests that signal transmission by the kelch repeat proteins occurs by altering the subcellular distribution of PKA. Current work is focused on identifying the ligand for the receptor and on defining the entire pathway that transmits the signal downstream of the Gpa2 a-subunit.