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The eIF‐2α kinases and the control of protein synthesis 1
Author(s) -
De Haro César,
Méndez Raúl,
Santoyo Javier
Publication year - 1996
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.10.12.8903508
Subject(s) - kinase , phosphorylation , protein kinase r , protein kinase a , protein phosphorylation , biochemistry , protein subunit , biology , protein biosynthesis , eif 2 kinase , integrated stress response , microbiology and biotechnology , translation (biology) , cyclin dependent kinase 2 , messenger rna , gene
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)