Phosphorylation of initiation factor 2 alpha by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast

Cell. 1992 Feb 7;68(3):585-96. doi: 10.1016/0092-8674(92)90193-g.


We show that phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2) by the protein kinase GCN2 mediates translational control of the yeast transcriptional activator GCN4. In vitro, GCN2 specifically phosphorylates the alpha subunit of rabbit or yeast eIF-2. In vivo, phosphorylation of eIF-2 alpha increases in response to amino acid starvation, which is dependent on GCN2. Substitution of Ser-51 with alanine eliminates phosphorylation of eIF-2 alpha by GCN2 in vivo and in vitro and abolishes increased expression of GCN4 and amino acid biosynthetic genes under its control in amino acid-starved cells. The Asp-51 substitution mimics the phosphorylated state and derepresses GCN4 in the absence of GCN2. Thus, an established mechanism for regulating total protein synthesis in mammalian cells mediates gene-specific translational control in yeast.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • DNA Mutational Analysis
  • DNA-Binding Proteins*
  • Fungal Proteins / genetics*
  • Humans
  • Infant, Newborn
  • Models, Genetic
  • Molecular Sequence Data
  • Oligonucleotide Probes
  • Open Reading Frames
  • Peptide Initiation Factors / metabolism*
  • Phosphorylation
  • Plasmids
  • Prokaryotic Initiation Factor-2
  • Protein Biosynthesis
  • Protein Kinases / metabolism*
  • Protein Serine-Threonine Kinases
  • Rabbits
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae Proteins*
  • Serine
  • Transcription Factors / genetics*


  • DNA-Binding Proteins
  • Fungal Proteins
  • Oligonucleotide Probes
  • Peptide Initiation Factors
  • Prokaryotic Initiation Factor-2
  • Saccharomyces cerevisiae Proteins
  • Transcription Factors
  • Serine
  • Protein Kinases
  • GCN2 protein, S cerevisiae
  • Protein Serine-Threonine Kinases