MULTIPLE SIGNALING PATHWAYS TRIGGER THE EXQUISITE SENSITIVITY OF YEAST GLUCONEOGENIC MESSENGER-RNAS TO GLUCOSE

The transcription of the yeast FBP1 and PCK1 genes, which encode the g luconeogenic enzymes fructose-1,6-bisphosphatase and phosphoenolpyruva te carboxykinase, is repressed by glucose. Here, we show that this rep ression is both very strong and exceptionally sensitive to glucose, be ing triggered by glucose at concentrations less than 0.005% (0.27 mM). This repression remains operative in yeast mutants carrying any one o f the three hexose kinases, but is lost in a triple hxk1, hxk2, glk1 m utant. In addition, 2-deoxyglucose can trigger the repression, but 6-d eoxyglucose cannot, suggesting that internalization and phosphorylatio n of the glucose is essential for repression to occur. While gluconeog enic gene transcription is subject to the Mig1 p-dependent pathway of glucose repression, the exquisite response to glucose is maintained in hxk2 and mig1 mutants, suggesting that this pathway is not essential for the response. The response can also be triggered by the addition o f exogenous cAMP, suggesting that the Ras/cAMP pathway can mediate rep ression of the FPB1 and PCK1 mRNAs, However, the response is not depen dent upon this pathway because it remains intact in Has, adenyl cyclas e and protein kinase A mutants. The data show that yeast cells can det ect very low glucose concentrations in the environment, and suggest th at several distinct signalling pathways operate to repress FPB1 and PC K1 transcription in the presence of glucose.