MOLECULAR CHARACTERIZATION OF SIG1, A SACCHAROMYCES-CEREVISIAE GENE INVOLVED IN NEGATIVE REGULATION OF G-PROTEIN-MEDIATED SIGNAL-TRANSDUCTION

Two recessive mutations in the Saccharomyces cerevisiae SIG1 (suppress or of inhibitory G-protein) gene have been identified by their ability to suppress the signalling defect of dominant-negative variants of th e mating response G-protein beta-subunit. The mutations and deletion o f SIG1 enhance the sensitivity of the cells to pheromone and stimulate the basal transcription of a mating specific gene, FUS1, suggesting t hat Sig1p plays a negatively regulatory role in G(beta gamma)-mediated signal transduction. An additional function of Sig1p in vegetatively growing cells is suggested by the finding that the mutations and delet ion of SIG1 cause temperature-sensitive growth defects. The SIG1 gene encodes a protein with a molecular weight of 65 kDa that contains at t he amino-terminus two zinc finger-like sequence motifs. Epistasis expe riments localize the action of Sig1p within the pheromone signalling p athway at a position at or shortly after the G-protein. We propose tha t Sig1p represents a novel negative regulator of G(beta gamma)-mediate d signal transduction.