FERMENTABLE SUGARS AND INTRACELLULAR ACIDIFICATION AS SPECIFIC ACTIVATORS OF THE RAS ADENYLATE-CYCLASE SIGNALING PATHWAY IN YEAST - THE RELATIONSHIP TO NUTRIENT-INDUCED CELL-CYCLE CONTROL

The RAS proteins of the yeast Saccharomyces cerevisiae fulfil a similar control function on yeast adenylate cyclase as the mammalian G(s) proteins on mammalian adenylate cyclase. The discovery that glucose and other fermentable sugars act as specific activators of the RAS-adenylate cyclase pathway in yeast appeared to offer a mechanism for the way in which at least one nutrient would control progression over the start point in the G1 phase of the yeast cell cycle by means of this pathway. Recently, however, evidence has been obtained to show that the glucose-activation pathway of adenylate cyclase is a glucose-repressible pathway and therefore not operative during growth on glucose. In addition, mutant strains were obtained which lack the glucose-activation pathway and show normal exponential growth on glucose. This appears to confine the physiological role of this pathway to control of the transition from the derepressed state (growth on respirative carbon sources) to the repressed state (growth on fermentative carbon sources) by means of an already well-documented cAMP-triggered protein phosphorylation cascade. Intracellular acidification also stimulates the RAS-adenylate cyclase pathway, which might constitute a rescue mechanism for cells suffering from stress conditions. The presence of a nitrogen source does not stimulate the RAS-adenylate cyclase pathway. Although other nutrient signals for the pathway might still be discovered, it appears more and more likely that the well-known requirement of cAMP for progression over the start point of the yeast cell cycle is limited to providing a basal cAMP level rather than acting as a second messenger for an extracellular signal. A model in which a nitrogen-source-induced pathway leads to activation of cAMP-dependent protein kinase synergistically with cAMP, or alternatively causes activation only of the free catalytic subunits, would provide an elegant explanation for the apparent contradiction that nitrogen-source induced progression over the start point of the yeast cell cycle does not seem to be mediated by cAMP but on the other hand seems to depend on cAMP and cAMP-dependent protein kinase.