title: Glucose repression/derepression in budding yeast: SNF1 protein kinase is activated by phosphorylation under derepressing conditions, and this correlates with a high AMP:ATP ratio.
abstract: BACKGROUND
  Genetic studies of Saccharomyces cerevisiae have shown that Snf1p and Snf4p, which together form the SNF1 complex, are essential for gene derepression on removal of glucose from the medium. However the metabolic signal(s) involved, and the exact role of SNF1, have remained enigmatic. Recently, the AMP-activated protein kinase (AMPK) was shown to be the mammalian homologue of SNF1. AMPK is activated by the elevation of the cellular AMP:ATP ratio, which occurs during cellular stress in mammalian cells. The mechanism of activation involves phosphorylation of AMPK by an upstream protein kinase (AMPKK). We have investigated whether a similar mechanism might explain the role of SNF1 in yeast in the response to the stress of glucose starvation.
  
  
  RESULTS
  The protein kinase activity of SNF1 was dramatically and rapidly activated by phosphorylation on removal of glucose from the medium. SNF1 was not activated directly by AMP, but could be inactivated by protein phosphatases and reactivated by mammalian AMPKK. We also demonstrated that an endogenous SNF1-reactivating factor, most likely an upstream protein kinase, is present in yeast extracts. Under a variety of different growth conditions, there was a correlation between cellular adenine nucleotide levels and the activation state of SNF1.
  
  
  CONCLUSIONS
  Apart from the lack of direct allosteric activation of SNF1 by AMP, the regulation of the mammalian AMPK and yeast SNF1 protein kinase cascades is highly conserved. Adenine nucleotides are now good candidates for metabolic signals which indicate the lack of glucose in the medium, triggering activation of SNF1 and derepression of glucose-repressed genes.
authors.affiliation: Biochemistry Department, The University, Dundee, Scotland, UK.
authors.forename: W A
authors.initials: WA
authors.lastname: Wilson
authors.forename: S A
authors.initials: SA
authors.lastname: Hawley
authors.forename: D G
authors.initials: DG
authors.lastname: Hardie
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000595:Amino Acid Sequence; D003470:Culture Media / Q000494:pharmacology; D004789:Enzyme Activation; D005947:Glucose / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism*
chemical_list: D003470:Culture Media; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases; D005947:Glucose