In the cAMP-dependent protein kinase A pathway antagonizes the cellular response to stress. It is shown here that the cellular content of Cdc25p, the upstream activator of Ras and adenylyl cyclase, decays upon various stresses such as heat shock and oxidative and ethanol shocks, whereas its phosphorylation level and its localization are unaffected. In parallel with the reduction of Cdc25p, the maximal capacity of the cell to accumulate cAMP decreases when its feedback regulation is abolished. A deletion of prevents this decrease. Paradoxically, in wild-type cells, with normal feedback regulation, the level of cAMP, which is much lower, is not reduced but is rather increased upon stress. These observations are consistent with a role of Cdc25p in sensing and transducing stress to downstream targets, either through a cAMP-independent pathway or by large fluctuations in the cAMP content of the cell.

Keyword(s): PKA, protein kinase A

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