Regulation and function of yeast PAS kinase: a role in the maintenance of cellular integrity.
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.
Grose
Julianne H
JH
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112-5650, USA. julianne_grose@byu.edu
Sundwall
Eleanor
E
Rutter
Jared
J
D000595:Amino Acid Sequence; D056827:Endosomal Sorting Complexes Required for Transport; D005947:Glucose / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D008969:Molecular Sequence Data; D009713:Nucleotidyltransferases / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D016415:Sequence Alignment; D033921:Vesicular Transport Proteins / Q000378:metabolism
D056827:Endosomal Sorting Complexes Required for Transport; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C425333:STP22 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C077016:TIM44 protein, S cerevisiae; D033921:Vesicular Transport Proteins; C116037:PAS domain kinases; D017346:Protein Serine-Threonine Kinases; D009713:Nucleotidyltransferases; D005947:Glucose