G-protein Coupled Receptors (GPCRs) comprise a large family of medically important receptors, which respond to a variety of signals, including hormones, neurotransmitters, ions and light. Proper regulation of GPCR function requires that they interact with many different proteins. Studying the proteins that interact with GPCRs has been difficult, in part, due to the hydrophobic nature of these membrane proteins. Therefore, I took advantage of the genetic accessibility of the yeast Saccharomyces cerevisiae to study proteins that interact with the alpha factor receptor, Ste2p, a GPCR responsible for the induction of the mating pathway. By implementing a two-hybrid system specifically designed for membrane proteins, I identified proteins that interact with Ste2p. Dimerization of Ste2p, as well as interaction of Ste2p with the regulatory proteins Afr1p and Sst2p was detected. Further analysis using this assay helped to demonstrate that some mutant forms of Afr1p and Sst2p were defective due to failure to bind to Ste2p. A second approach involved studying the mechanism by which GPCRs activate the next component in the signaling pathway, known as a heterotrimeric G protein. Residues in six regions of the alpha subunit of the G protein (Gpa1) predicted to be in close proximity to Ste2p were targeted for mutagenesis. Thirty-three different amino acid substitutions displayed a range of phenotypes from non-signaling to constitutive activation of the pheromone pathway, indicating many regions of Ga contribute to the interaction with the receptor. Altogether, these studies provide new insight into the function of the proteins that regulate GPCR signaling and to the ability of GPCRs to activate heterotrimeric G proteins.