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Elm1p is one of three upstream kinases for the Saccharomyces cerevisiae SNF1 complex

Elm1p is one of three upstream kinases for the Saccharomyces cerevisiae SNF1 complex

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Authors

  • Catherine M. Sutherland
  • Simon A. Hawley
  • Rhonda R. McCartney
  • Anna Leech
  • Michael J. R. Stark
  • Martin C. Schmidt
  • D. Grahame Hardie

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Original languageEnglish
Pages1299-1305
Number of pages7
JournalCurrent Biology
Journal publication date5 Aug 2003
Volume13
Issue15
DOIs
StatePublished

Abstract

Background: The yeast SNF1 protein kinase and the mammalian AMP-activated protein kinase are highly conserved heterotrimeric complexes that are "metabolic master switches" involved in the switch from fermentative/anaerobic to oxidative metabolism. They are activated by cellular stresses that deplete cellular ATP, and SNF1 is essential in the response to glucose starvation. In both cases, activation requires phosphorylation at a conserved threonine residue within the activation loop of the kinase domain, but identifying the upstream kinase(s) responsible for this has been a challenging, unsolved problem. Results: Using a library of strains that express 119 yeast protein kinases as GST fusions, we identified Elm1p as the sole kinase that could activate the kinase domain of AMP-activated protein kinase in vitro. Elm1p also activated the purified SNF1 complex, and this correlated with phosphorylation of Thr210 in the activation loop. Removal of the C-terminal domain increased the Elm1p kinase activity, indicating that it is auto-inhibitory. Expression of activated, truncated Elm1p from its own promoter gave a constitutive pseudohyphal growth phenotype that was rescued by deletion of SNF1, showing that Snf1 p was acting downstream of Elm1p. Deletion of ELM1 does not give an snf- phenotype. However, Elm1p is closely related to Pak1p and Tos3p, and a pak1? tos3? elm1? triple mutant had an snf1- phenotype, i.e., it would not grow on raffinose and did not display hyperphosphorylation of the SNF1 target, Mig1p, in response to glucose starvation. Conclusions: Elm1p, Pak1p, and Tos3p are upstream kinases for the SNF1 complex that have partially redundant functions.

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