Guanine nucleotide-binding protein alpha-1 subunit

UniProtKB accession:  P08539

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UniProtKB description:  Alpha subunit of the heterotrimeric guanine nucleotide-binding protein (G protein) that mediates mating pheromone signal transduction. Binding of alpha-factor or a-factor to its cognate transmembrane receptor STE2 and STE3, respectively, allows the receptor to serve as a guanine nucleotide exchange factor (GEF) on GPA1. The exchange of GDP for GTP on the G protein alpha subunit alters its interaction with the G protein beta subunit STE4, leading to dissociation of the G protein beta-gamma dimer STE4-STE18. The dissociated subunits activate downstream effectors to activate the mating response pathway and induce changes necessary to produce mating-competent cells. STE4-STE18 activate the downstream pheromone signaling MAP kinase cascade leading to expression of mating-specific genes, inducing cell cycle arrest in G1, promoting polarized cell growth to form mating projections (shmoos), and establishing the changes in plasma membrane, cell wall and nuclear envelope to permit cell-cell fusion (plasmogamy) and fusion of the two haploid nuclei (karyogamy). GPA1 transmits a signal that requires direct binding to the effector enzyme PI3K located at the endosome, promoting increased PI3 production. The intrinsic GTPase activity of GPA1 determines the duration of signaling, and is dramatically accelerated by the RGS protein SST2. In unstimulated cells, GDP-bound GPA1 sequesters the G protein beta-gamma subunit STE4-STE18, preventing it from activating the downstream effectors. Also down-regulates the signal by inhibiting the pheromone-induced accumulation of FUS3 in the nucleus.