Cell. 1992 Feb 7;68(3):585-96.

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

Dever TE, Feng L, Wek RC, Cigan AM, Donahue TF, Hinnebusch AG.

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Section on Molecular Genetics of Lower Eukaryotes, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.

Abstract

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.

PMID:: 1739968; [PubMed - indexed for MEDLINE]

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GCN1, a translational activator of GCN4 in Saccharomyces cerevisiae, is required for phosphorylation of eukaryotic translation initiation factor 2 by protein kinase GCN2. [Mol Cell Biol. 1993]
GCN1, a translational activator of GCN4 in Saccharomyces cerevisiae, is required for phosphorylation of eukaryotic translation initiation factor 2 by protein kinase GCN2.
Marton MJ, Crouch D, Hinnebusch AG. Mol Cell Biol. 1993 Jun; 13(6):3541-56.
Mammalian eukaryotic initiation factor 2 alpha kinases functionally substitute for GCN2 protein kinase in the GCN4 translational control mechanism of yeast. [Proc Natl Acad Sci U S A. 1993]
Mammalian eukaryotic initiation factor 2 alpha kinases functionally substitute for GCN2 protein kinase in the GCN4 translational control mechanism of yeast.
Dever TE, Chen JJ, Barber GN, Cigan AM, Feng L, Donahue TF, London IM, Katze MG, Hinnebusch AG. Proc Natl Acad Sci U S A. 1993 May 15; 90(10):4616-20.
Review Gene-specific translational control of the yeast GCN4 gene by phosphorylation of eukaryotic initiation factor 2. [Mol Microbiol. 1993]
Review Gene-specific translational control of the yeast GCN4 gene by phosphorylation of eukaryotic initiation factor 2.
Hinnebusch AG. Mol Microbiol. 1993 Oct; 10(2):215-23.
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GCN20, a novel ATP binding cassette protein, and GCN1 reside in a complex that mediates activation of the eIF-2 alpha kinase GCN2 in amino acid-starved cells.
Vazquez de Aldana CR, Marton MJ, Hinnebusch AG. EMBO J. 1995 Jul 3; 14(13):3184-99.
Review Translational control of GCN4: an in vivo barometer of initiation-factor activity. [Trends Biochem Sci. 1994]
Review Translational control of GCN4: an in vivo barometer of initiation-factor activity.
Hinnebusch AG. Trends Biochem Sci. 1994 Oct; 19(10):409-14.

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