Increased phosphoglucomutase activity suppresses the galactose growth defect associated with elevated levels of Ras signaling in S. cerevisiae.
The Ras proteins regulate many aspects of cell growth in the budding yeast, Saccharomyces cerevisiae, via the cAMP-dependent protein kinase (PKA). Here, we show that a RAS2(val19) mutant that exhibits elevated levels of Ras/PKA signaling activity is unable to grow on media with galactose as the sole source of carbon. This growth defect was due, at least in part, to a defect in the expression of genes, like GAL1, that encode enzymes needed for the metabolism of galactose. This growth defect was used as the basis for a genetic screen for dosage suppressors of the RAS2(val19) mutant. This screen identified two genes, PGM1 and PCM1, that encode proteins with phosphoglucomutase activity. This activity is responsible for converting the glucose-1-phosphate produced during the metabolism of galactose to glucose-6-phosphate, a precursor that can be metabolized via the glycolytic pathway. The over-expression of PGM1 was not able to suppress any other RAS2(val19) phenotype or the galactose growth defect associated with a gal1Delta mutant. Overall, these data suggest that the elevated levels of phosphoglucomutase activity allow for the more efficient utilization of the limiting levels of glucose-1-phosphate that are present in the RAS2(val19) mutant.
Howard
Susie C
SC
Department of Molecular Genetics, The Ohio State University, 484 West Twelfth Avenue, Room 984, Columbus, 43210, USA.
Deminoff
Stephen J
SJ
Herman
Paul K
PK
D003470:Culture Media; D005690:Galactose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005952:Glucose-6-Phosphatase / Q000378:metabolism; D005958:Glucosephosphates / Q000378:metabolism; D010733:Phosphoglucomutase / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000254:growth & development* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics* / Q000378:metabolism
D003470:Culture Media; D005958:Glucosephosphates; D029701:Saccharomyces cerevisiae Proteins; C031590:glucose-1-phosphate; D005952:Glucose-6-Phosphatase; C489015:RAS2 protein, S cerevisiae; D018631:ras Proteins; D010733:Phosphoglucomutase; D005947:Glucose; D005690:Galactose