Identification of PAS kinase activators

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DESCRIPTION (provided by applicant): Cells have evolved complex mechanisms to sense their nutritional environment and regulate growth and proliferation accordingly. Failure to properly coordinate cellular metabolism results in a variety of human diseases and syndromes. PAS kinase plays a critical role in coordinating metabolism by sensing cellular metabolic status and regulating sugar metabolism. PAS kinase is a serine/threonine protein kinase regulated in cis by a small molecule-binding PAS domain. Although the biologically relevant ligand is unknown, two stimuli have been identified that lead to activation of PAS kinase in S. cerevisiae: first, growth in non-fermentable carbon sources and, second, cell integrity stress. Both biochemical and genetic techniques will be used to identify factors involved in PAS kinase activation in response to both stimuli. This knowledge will aid in understanding how PAS kinase coordinates cell growth and proliferation in response to environmental nutrients and stresses.