Coordinate regulation of sugar flux and translation by PAS kinase.
PAS kinase is a serine/threonine kinase regulated in cis by a PAS domain. A genetic study of the two PAS kinase genes in budding yeast gave evidence of the involvement of these enzymes in the control of sugar metabolism and translation. Using a biochemical screen for PAS kinase substrates, three translation factors were identified as direct phosphorylation targets. PAS kinase was also found to phosphorylate UDP-glucose pyrophosphorylase and glycogen synthase, the enzymes catalyzing the two final steps in the glycogen biosynthetic pathway. Genetic, biochemical, and physiological data provide evidence that both of these enzymes are inhibited by PAS kinase-dependent phosphorylation, thereby downregulating carbohydrate storage. These studies provide evidence of a cell-autonomous signaling system that both controls and connects the balance of fuel consumption/storage to protein synthesis.
Rutter
Jared
J
Department of Biochemistry, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA.
Probst
Brandon L
BL
McKnight
Steven L
SL
D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D050260:Carbohydrate Metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D015971:Gene Expression Regulation, Enzymologic; D005822:Genetic Vectors; D005838:Genotype; D006006:Glycogen Synthase / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008954:Models, Biological; D009154:Mutation; D010641:Phenotype; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D014176:Protein Biosynthesis; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism; D015398:Signal Transduction; D013379:Substrate Specificity; D013489:Suppression, Genetic; D005957:UTP-Glucose-1-Phosphate Uridylyltransferase / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D006006:Glycogen Synthase; D011494:Protein Kinases; C467888:PSK1 protein, S cerevisiae; C116037:PAS domain kinases; C467889:PSK2 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; D005957:UTP-Glucose-1-Phosphate Uridylyltransferase