The inability to coordinate cellular metabolic processes with the cellular and organismal nutrient environment leads to a variety of disorders, including diabetes and
obesity. Nutrient-sensing
protein kinases, such as AMPK and mTOR, play a pivotal role in metabolic regulation and are promising therapeutic targets for the treatment of disease. In this Extra View, we describe another member of the nutrient-sensing
protein kinase group,
PAS kinase, which plays a role in the regulation of
glucose utilization in both mammals and yeast.
PAS kinase deficient mice are resistant to high fat diet-induced
weight gain,
insulin resistance and hepatic
triglyceride hyperaccumulation, suggesting a role for
PAS kinase in the regulation of
glucose and lipid metabolism in mammals. Likewise,
PAS kinase deficient yeast display altered
glucose partitioning, favoring
glycogen biosynthesis at the expense of cell wall biosynthesis. As a result,
PAS kinase deficient yeast are sensitive to cell wall perturbing agents. This partitioning of
glucose in response to
PAS kinase activation is due to phosphorylation of Ugp1, the
enzyme primarily responsible for
UDP-glucose production. The two yeast
PAS kinase homologs, Psk1 and Psk2, are activated by two stimuli, cell integrity stress and nonfermentative
carbon sources. We review what is known about yeast
PAS kinase and describe a genetic screen that may help elucidate pathways involved in
PAS kinase activation and function.