The eIF-2 alpha kinases and the control of protein synthesis

被引:242
作者
deHaro, C
Mendez, R
Santoyo, J
机构
[1] Ctr. de Biol. Molec. Severe Ochoa, Consejo Sup. de Invest. Cientfficas, Univ. Autónoma de Madrid
[2] Ctro. de Biol. Molec. Severo Ochoa, CSIC-UAM, Facultad de Ciencias, Canto Blanco
[3] Department of Biochemistry, Louisiana State University, Medical Center, Shreveport
关键词
protein-serine kinase; protein phosphorylation; translational control; eIF-2; alpha; cell cycle;
D O I
10.1096/fasebj.10.12.8903508
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein synthesis is regulated in response to environmental stimuli by covalent modification, primarily phosphorylation, of components of the translational machinery. Phosphorylation of the alpha 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 alpha subunit of eIF-2 at serine-51. There are two mammalian eIF-2 alpha 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-2 alpha 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-deficient conditions. Yeast GCN2 is activated by amino acid starvation. The phosphorylation of eIF-2 alpha results in the shutdown of protein synthesis. Nevertheless, the eIF-2 alpha kinases can regulate both global as well as specific mRNA translation. inhibition of protein synthesis correlates with eIF-2 alpha 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-2 alpha phosphorylation in the control of cell growth and differentiation.
引用
收藏
页码:1378 / 1387
页数:10
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