Phosphorylation of the S. cerevisiae Cdc25 in response to glucose results in its dissociation from Ras

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Abstract
IN the yeast Sacchromyces cerevisiae, addition of glucose to starved cells triggers a transient rise in the intracellular level of cyclic AMP that induces a protein phosphorylation cascade1. The glucose signal is processed by the Cdc25/Ras/adenylyl cyclase pathway2, where the role of Cdc25 is to catalyse the GDP–GTP exchange on Ras3. The molecular mechanisms involved in the regulation of the activity of Cdc25 are unknown. We report here the use of highly selective anti-Cdc25 antibodies4 to demonstrate that Cdc25 is a phospho protein and that in response to glucose it is hyper-phosphorylated, within seconds, by the cyclic AMP-dependent protein kinase. It is also demonstrated that, concomitantly with hyperphosphorylation, Cdc25 partially relocalizes to the cytoplasm, reducing its accessibility to membrane-bound Ras. These results are of general significance because of the highly conserved sequence of Ras–guanyl nucleotide exchange factors from yeasts to mammals.