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Efficient transition to growth on fermentable carbon sources in Saccharomyces cerevisiae requires signaling through the Ras pathway

Strains carrying ras2318S as their sole RAS gene fail to elicit a transient increase in cAMP levels following addition of glucose to starved cells but maintain normal steady‐state levels of cAMP under a variety of growth conditions. Such strains show extended delays in resuming growth following transition from a quiescent state to glucose‐containing growth media, either in emerging from stationary phase or following inoculation as spores onto fresh media. Otherwise, growth of such strains is indistinguishable from that of RAS2+ strains. ras2318S strains also exhibit a delay in glucose‐stimulated phosphorylation and turnover of fructose‐1,6‐bisphosphatase, a substrate of the cAMP‐dependent protein kinase A (PKA) and a key component of the gluconeogenic branch of the glycolytic pathway. Finally Tpkw strains, which fail to modulate PKA in response to fluctuations in cAMP levels, show the same growth delay phenotypes, as do ras2318S strains. These observations indicate that the glucose‐induced cAMP spike results in a transient activation of PKA, which is required for efficient transition of yeast cells from a quiescent state to resumption of rapid growth. This represents the first demonstration that yeast cells use the Ras pathway to transmit a signal to effect a biological change in response to an upstream stimulus.