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Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12578-83.

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

Author information

1
Howard Hughes Medical Institute, and Departments of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.

Abstract

In addition to its well-established role in responding to phosphate starvation, the cyclin-dependent kinase Pho85 has been implicated in a number of other 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 that enabled us to control Pho85 kinase activity with a cell-permeable inhibitor 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 to environmental stress. In addition, we show that the effects of this inhibitor are both rapid and reversible, making it well suited to the study of the behavior of dynamic signaling pathways.

PMID:
11675494
PMCID:
PMC60096
DOI:
10.1073/pnas.211195798
[Indexed for MEDLINE]
Free PMC Article

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