Fus3

Fus3 is a mitogen-activated protein kinase (MAPK) in the budding yeast Saccharomyces cerevisiae and a central component of the pheromone response pathway. As a member of the ERK-like MAPK family, Fus3 transduces signals from pheromone-activated G protein–coupled receptors to regulate mating-related transcription, cell-cycle arrest, and morphological changes such as shmoo formation.

Activation and signaling context: Fus3 is activated downstream of the MAPKK Ste7 and, in the presence of the Ste5 scaffold, localizes to the membrane to receive signals from Ste11 (the MAPKKK). Activation involves dual phosphorylation on a conserved TXY motif in the activation loop. Once active, Fus3 phosphorylates substrates including the transcription factor Ste12, promoting pheromone-induced gene expression, and Far1, which links the pheromone signal to the polarity machinery via Cdc42 to drive mating projection formation. The pheromone response pathway is subject to regulation and cross-talk, with the related MAPK Kss1 involved in alternative growth programs under different conditions.

Function and phenotype: FUS3 mutants exhibit defects in pheromone signaling, fail to arrest the cell cycle in G1, and do not form mating projections, while appropriate Fus3 activity is necessary for a full mating response. Fus3's activity is coordinated with the Ste5 scaffold and interacts with other pathway components to ensure specificity of the mating response and to distinguish it from other MAPK-mediated programs in yeast.

See also: MAPK cascade, Ste5, Ste12, Far1, FUS3 gene.