The eIF-2α kinases and the control of protein synthesis1

César De Haro, Raúl Méndez, Javier Santoyo

Research output: Contribution to journalReview articlepeer-review

Abstract / Description of output

Protein synthesis is regulated in response to environmental stimuli by covalent modification, primarily phosphorylation, of components of the tranelational machinery. Phosphorylation of the α subunit of eIF-2 is one of the best-characterized mechanisms for down-regulating protein synthesis in higher eukaryotes in response to various stress conditions. Three distinct protein kinases regulate protein synthesis in eukaryotic cells by phosphorylating the α subunit of eIF-2 at serine-51. There are two mammalian eIF-2α kinases: the double-stranded RNA-dependent kinase (PKR) and heme-regulated inhibitor kinase (HRI), and the yeast GCN2. The regulatory mechanisms and the molecular sizes of these eIF-2α kinases are different. The expression of PKR is induced by interferon, and the kinase activity is stimulated by low concentrations of double-stranded RNA. HRI is activated under heme-defi-cient conditions. Yeast GCN2 is activated by amino acid starvation. The phosphorylation of eIF-2α results in the shutdown of protein synthesis. Nevertheless, the eIF-2α kinases can regulate both global as well as specific mRNA translation. Inhibition of protein synthesis correlates with eIF-2α phosphorylation in response to a wide variety of different stimuli, including heat shock, serum deprivation, glucose starvation, amino acid starvation, exposure to heavy metal ions, and viral infection. Finally, recent studies suggest a role for eIF-2α phosphorylation in the control of cell growth and differentiation.—de Haro, C., Méndez, R., Santoyo, J. The eIF-2α kinases and the control of protein synthesis. FASEB J. 10, 1378-1387(1996)
Original languageEnglish
Pages (from-to)1378-1387
Number of pages10
JournalThe FASEB Journal
Volume10
Issue number12
DOIs
Publication statusPublished - 1 Oct 1996

Keywords / Materials (for Non-textual outputs)

  • cell cycle
  • eIF-2α
  • protein phosphorylation
  • protein-serine kinase
  • translational control

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