Regulation of glucose partitioning by PAS kinase and Ugp1 phosphorylation

Mol Cell. 2007 May 25;26(4):491-9. doi: 10.1016/j.molcel.2007.03.025.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Wall / enzymology
  • Glucose / metabolism*
  • Glycogen / biosynthesis*
  • Homeostasis
  • Phosphorylation
  • Protein Conformation
  • Protein Serine-Threonine Kinases / metabolism*
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • UTP-Glucose-1-Phosphate Uridylyltransferase / chemistry
  • UTP-Glucose-1-Phosphate Uridylyltransferase / metabolism*

Substances

  • Saccharomyces cerevisiae Proteins
  • Glycogen
  • PAS domain kinases
  • Protein Serine-Threonine Kinases
  • UTP-Glucose-1-Phosphate Uridylyltransferase
  • Glucose