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 (Delta cnb1 Delta 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 Delta cnb1 Delta 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.
Department of Molecular Biotechnology, Graduate School of Advanced Sciences of Matter, Hiroshima University, Higashi-Hiroshima 739-8530, Japan.
Atsunori
A
Shitamukai
Dai
D
Hirata
Shinya
S
Sonobe
Tokichi
T
Miyakawa
D000199:Actins / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002453:Cell Cycle; D002455:Cell Division; D002469:Cell Separation; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins; D005434:Flow Cytometry; D016195:G2 Phase; D017353:Gene Deletion; D005838:Genotype; D005990:Glycerol / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008938:Mitosis; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D000071636:Protein Phosphatase 2C; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors
D000199:Actins; C109868:CRZ1 protein, S cerevisiae; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; D019703:Calcineurin; C000607465:PTC4 protein, S cerevisiae; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C; D005990:Glycerol; D002118:Calcium