Evidence for Antagonistic Regulation of Cell Growth by the Calcineurin and High Osmolarity Glycerol Pathways in Saccharomyces cerevisiae

Because Ca 2+ signaling of budding yeast, through the activation of calcineurin and the Mpk1/Slt2 mitogen-activated protein kinase cascade, performs redundant function(s) in the events essential for growth, the simultaneous deletion of both these pathways (Δ cnb1 Δ mpk1 ) leads to lethality. A PTC4 cDNA that encodes a protein phosphatase belonging to the PP2C family was obtained as a high dosage suppressor of the lethality of Δ cnb1 Δ mpk1 strain. Overexpression of PTC4 led to a decrease in the high osmolarity-induced Hog1 phosphorylation, and HOG1 deletion remarkably suppressed the synthetic lethality, indicating an antagonistic role of the high osmolarity glycerol (HOG) pathway and the Ca 2+ signaling pathway in growth regulation. The calcineurin-Crz1 pathway was required for the down-regulation of the HOG pathway. Analysis of the time course of actin polarization, bud formation, and the onset of mitosis in synchronous cell cultures demonstrated that calcineurin negatively regulates actin polarization at the bud site, whereas the HOG pathway positively regulates bud formation at a later step after actin has polarized.