The RACK1 ortholog Asc1 functions as a G-protein β subunit coupled to glucose responsiveness in yeast

According to the prevailing paradigm, G- proteins are composed of three subunits, an alpha subunit with GTPase activity and a tightly associated beta gamma subunit complex. In the yeast Saccharomyces cerevisiae there are two known G alpha proteins ( Gpa1 and Gpa2) but only one G beta gamma, which binds only to Gpa1. Here we show that the yeast ortholog of RACK1 ( receptor for activated protein kinase C1) Asc1 functions as the G beta for Gpa2. As with other known G beta proteins, Asc1 has a 7-WD domain structure, interacts directly with the G alpha in a guanine nucleotide-dependent manner, and inhibits G alpha guanine nucleotide exchange activity. In addition, Asc1 binds to the effector enzyme adenylyl cyclase ( Cyr1), and diminishes the production of cAMP in response to glucose stimulation. Thus, whereas Gpa2 promotes glucose signaling through elevated production of cAMP, Asc1 has opposing effects on these same processes. Our findings reveal the existence of an unusual G beta subunit, one having multiple functions within the cell in addition to serving as a signal transducer for cell surface receptors and intracellular effectors.