Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, U.S.A.
| In yeast, the mating response pathway is activated when a peptide pheromone binds to a heterotrimeric guanine nucleotide–binding protein (G protein)—coupled receptor, which leads to the activation of a mitogen-activated protein kinase signaling cascade and the stimulation of mating behavior. However, when nutrients in the environment are limiting, stimulation of the mating response would be maladaptive. A study indicates that the signaling pathways that respond to nutrient availability dampen the mating response by directly phosphorylating Gpa1, the G protein α subunit that initiates the mating response pathway. Snf1, the yeast homolog of adenosine monophosphate–activated protein kinase, is a highly conserved kinase that maintains energy homeostasis in response to nutrient limitation. The study found that the upstream kinases and phosphatase that control the activity of Snf1 also act on Gpa1 and provide a direct means to coordinate cell behavior and integrate the mating response with nutrient sensing. |
| Fig. 1. Crosstalk between the signaling pathways that mediate nutrient sensing and the mating response. The mating response pathway is initiated when the pheromone α factor binds to the GPCR Ste2 at the plasma membrane. Ligand binding stimulates the exchange of GDP for GTP by Gpa1 and the dissociation of Gpa1 from the Ste4- Ste18 dimer of the G protein. Ste4-Ste18 interacts with Ste20 to stimulate the MAPK signaling cascade, culminating in the activation of Fus3 and the mating response. During conditions of glucose abundance, the Ras and Gpa2 pathways activate PKA, which promotes the Glc7- Reg1–dependent dephosphorylation of Gpa1 to maintain an effi cient mating response. However, when glucose concentrations are limiting, PKA and the Glc7-Reg1 phosphatase complex are inactivated. Thus, the kinase Sak1 phosphorylates both Snf1 (the AMPK homolog), to initiate metabolic adaptation, and the Gpa1 protein, to reduce mating effi ciency. The exact consequences of Gpa1 phosphorylation on G protein signaling remain to be determined. |