Chemical inhibition of the Pho85 cyclin-dependent kinase reveals a role inthe environmental stress response

In addition to its well-established role in responding to phosphate starvat ion, the cyclin-dependent kinase Pho85 has been implicated in a number of o ther physiological responses of the budding yeast Saccharomyces cerevisiae, including synthesis of glycogen. To comprehensively characterize the range of Pho85-dependent gene expression, we used a chemical genetic approach th at enabled us to control Pho85 kinase activity with a cell-permeable inhibi tor and whole genome transcript profiling. We found significant phenotypic differences between the rapid loss of activity caused by inhibition and the deletion of the genomic copy of PHO85. We demonstrate that Pho85 controls the expression of not only previously identified glycogen synthetic genes, but also a significant regulon of genes involved in the cellular response t o environmental stress. in addition, we show that the effects of this inhib itor are both rapid and reversible, making it well suited to the study of t he behavior of dynamic signaling pathways.