The SH3-domain protein Bem1 coordinates mitogen-activated protein kinase cascade activation with cell cycle control in Saccharomyces cerevisiae

The mating mitogen-activated protein kinase (MAPK) cascade has three major outputs prior to fusion: transcriptional activation of many genes, cell cycle arrest in the G₁ phase, and polarized growth. Bem1 localizes near the cortical actin cytoskeleton and is essential for polarized growth during mating. Here we show that Bem1 is required for efficient signal transduction and coordinates MAPK cascade activation with G₁ arrest and mating. bem1Δ null mutants are defective in G₁ arrest and transcriptional activation in response to mating pheromone. Bem1 protein stimulates Fus3 (MAPK) activity and associates with Ste5, the tethering protein essential for activation of the MAPK kinase kinase Ste11. Bem1-Ste5 complexes also contain Ste11, Ste7 (MAPK kinase), and Fus3, suggesting that Ste5 localizes the MAPK cascade to Bem1. Strikingly, Bem1 also copurifies with Far1, a Fus3 substrate required for G₁ arrest and proper polarized growth during mating. These and other results suggest that Bem1 may cross-link the Ste5-MAPK cascade complex to upstream activators and specific downstream substrates at the shmoo tip, thus enabling efficient circuitry for G₁ arrest and mating.