Regulation of glucose partitioning by PAS kinase and Ugp1 phosphorylation.
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.
Smith
Tammy L
TL
Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT 84112, USA.
Rutter
Jared
J
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*
D029701:Saccharomyces cerevisiae Proteins; D006003:Glycogen; C116037:PAS domain kinases; D017346:Protein Serine-Threonine Kinases; D005957:UTP-Glucose-1-Phosphate Uridylyltransferase; D005947:Glucose