title: Regulation of glucose partitioning by PAS kinase and Ugp1 phosphorylation.
abstract: The ability of cells to recognize and respond to specific metabolic deficiencies is required for all forms of life. We have uncovered a system in the yeast S. cerevisiae that, in response to a perceived deficiency in cell wall glucan, alters partitioning of glucose toward glucan synthesis and away from glycogen synthesis. The paralogous yeast PAS kinases Psk1 and Psk2 phosphorylate UDP-glucose pyrophosphorylase (Ugp1), the primary producer of UDP-glucose, the glucose donor for glucan biosynthesis. Unexpectedly, phosphorylation of Ugp1 does not affect its catalytic activity but instead alters the terminal destination of the UDP-glucose it generates. Phosphorylated Ugp1 is required for intensive glucan production, and inability to phosphorylate Ugp1 is associated with a weak cell wall, decreased glucan content, and increased glycogen content. We provide data indicating that phosphorylation by Psk1 or Psk2 targets Ugp1 to the cell periphery, where the UDP-glucose it produces is in proximity to the site of glucan synthesis. We propose that regulation of glucose partitioning by altered enzyme and substrate localization is a rapid and potent response to metabolic deficiency.
authors.affiliation: Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Smith
authors.forename: Jared
authors.initials: J
authors.lastname: Rutter
mesh_terms: D002473:Cell Wall / Q000201:enzymology; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis*; D006706:Homeostasis; D010766:Phosphorylation; D011487:Protein Conformation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D005957:UTP-Glucose-1-Phosphate Uridylyltransferase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D006003:Glycogen; C116037:PAS domain kinases; D017346:Protein Serine-Threonine Kinases; D005957:UTP-Glucose-1-Phosphate Uridylyltransferase; D005947:Glucose