Abstract
With the increasing intensity of research into the processes of translation, it has become apparent that this phase of gene expression is often tightly regulated. Alteration of the phosphorylation state of an essential protein appears to be the predominant method that cells use to regulate biochemical activity, so it is no surprise that many of the steps in the translational pathway can be regulated by phosphorylation or dephosphorylation. Nevertheless, the linkage between such changes in covalent modification and modulation of enzymatic activity has been established in vivo for only three proteins (Hershey, 1990): eukaryotic elongation factor 2 (eEF-2), eukaryotic initiation factor 4E (elF-4E), and eukaryotic initiation factor 2 (elF-2). In mitosis eEF-2 is phosphorylated, resulting in an inhibition of translation because of an inability of the phosphorylated form of eEF-2 to catalyze the translocation of the peptidyl-tRNA during polypeptide chain elongation. The protein elF-4E is an essential component of the cap binding complex, elF-4F, which is responsible for bringing the 40S ribosomal subunit to the methylated cap of mRNA during translation. If elF-4E is dephosphorylated, as occurs during heat shock and mitosis, the elF-4F complex fails to deliver the ribosomal subunit to the mRNA. The best understood mode of translation control, however, involves the phosphorylation of the α subunit of elF-2.
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References
Bhat, R.A. and Thimmappaya, B. (1985). Construction and analysis of additional adenovirus substitution mutants confirm the complementation of VAI RNA function by two small RNAs encoded by Epstein-Barr virus. J. Virol. 56, 750–756.
Dubois, M.-F., Galabru, J., Lebon, P., Safer, B., and Hovanessian, A.G. (1989). Reduced activity of the interferon-induced double-stranded RNA-dependent protein kinase during a heat shock stress. J. Biol. Chem. 264, 12165–12171.
Galabru, J., Katze, M.G., Robert, N., and Hovanessian, A.G. (1989). The binding of double-stranded RNA and adenovirus VAI RNA to the interferon-induced protein kinase. Eur. J. Biochem. 178,581–589.
Green, S.R. and Mathews, M.B. (1992). Two RNA binding motifs in the double-stranded RNA activated protein kinase, DAI. Genes Dev. 6, 2478–2490.
Gunnery, S., Green, S.R., and Mathews, M.B. (1992). HIV-1 TAR RNA stimulates protein synthesis in vivo and in vitro: Relationship between structure and function. Proc. Natl. Acad. Sci. USA 89, 11557–11561.
Hanks, S.K., Quinn, A.M., and Hunter, T. (1988). The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science 241, 42–52.
Hershey, J.W.B. (1989). Protein phosphorylation controls translation rates. J. Biol. Chem. 264, 20823–20826.
Hershey, J.W.B. (1990). Overview: Phosphorylation and Translational Control. In Translationally regulated genes in higher eukaryotes. R.E. Thach, ed. (Basel: S. Karger), pp. 17–27.
Hershey, J.W.B. (1991). Translational control in mammalian cells. Annu. Rev. Biochem. 60, 717–755.
Hinnebusch, A.G. (1990). Involvement of an initiation factor and protein phosphorylation in translational control of GCN4 mRNA. TIBS 15, 148–152.
Jackson, R.J. (1991). Binding of Met-tRNA. In Translation in eukaryotes. H. Trachsel, ed. (Boca Raton, USA: CRC Press), pp. 193–230.
Katze, M.G., Wambach, M., Wong, M.-L, Garfinkel, M., Meurs, E., Chong, K., Williams, B.R.G., Hovanessian, A.G., and Barber, G.N. (1991). Functional expression and RNA binding analysis of the interferon-induced, double-stranded RNA-activated, 68,000–Mr protein kinase in a cell-free system. Mol. Cell. Biol. 11, 5497–5505.
Koromilas, A.E., Roy, S., Barber, G.N., Katze, M.G., and Sonenberg, N. (1992). Malignant transformation by a mutant of the IFN-inducible dsRNA-dependent protein kinase. Science 257, 1685–1689.
Kostura, M. and Mathews, M.B. (1989). Purification and activation of the double-stranded RNA-dependent elF-2 kinase DAI. Mol. Cell. Biol. 9, 1576–1586.
Manche, L., Green, S.R., Schmedt, C, and Mathews, M.B. (1992). Interactions between double-stranded RNA regulators and the protein kinase DAI. Mol. Cell. Biol. 12, 5238–5248.
Mathews, M.B. (1993). Seminars in Virology (Philadelphia: Saunders).
Mathews, M.B. and Shenk, T. (1991). Adenovirus virus-associated RNA and translational control. J. Virol. 65, 5657–5662.
McCormack, S.J., Thomis, D.C., and Samuel, CE. (1992). Mechanism of interferon action: Identification of a RNA binding domain within the N-terminal region of the human RNA-dependent P 1/eIF-2a protein kinase. Virology 188, 47–56.
Meurs, E., Chong, K., Galabru, J., Thomas, N.S.B., Kerr, I.M., Williams, B.R.G., and Hovanessian, A.G. (1990). Molecular cloning and characterization of the human double-stranded RNA-activated protein kinase induced by interferon. Cell 62, 379–390.
Moldave, K. (1985). Eukaryotic protein synthesis. Ann. Rev. Biochem. 54,1109–1149.
Pain, V.M. (1986). Initiation of protein synthesis. Biochem. J. 235, 625–637.
Patel, R.C. and Sen, G.C. (1992). Identification of the double-stranded RNA-binding domain of the human interferon-inducible protein kinase. J. Biol. Chem. 267, 7671–7676.
Petryshyn, R., Chen, J.-J., and London, I.M. (1984). Growth-related expression of a double-stranded RNA-dependent protein kinase in 3T3 cells. J. Biol. Chem. 259, 14736–14742.
Proud, C.G. (1986).Guanine nucleotides, protein phosphorylation and the control of translation. Trends in Biochem.Sci. 11,73–77.
Proud, CG. (1986). Guanine nucleotides, protein phosphorylation and the control of translation. Trends in Biochem. Sci. 11, 73–77. Sonenberg, N. (1990). Measures and countermeasures in the modulation of initiation factor activities by viruses. New Biol. 2, 402–409.
Wek, R.C, Ramirez, M., Jackson, B.M., and Hinnebusch, A.G. (1990). Identification of positive-acting domains in GCN2 protein kinase required for translational activation of GCN4 expression. Mol. Cell. Biol. 10, 2820–2831.
Zinn, K., Keller, A., Whitemore, L.-A., and Maniatis, T. (1988). 2-aminopurine selectively inhibits the induction of ß-interferon, c-fos, c-myegene expression. Science 240, 210–213.
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Green, S.R., Mathews, M.B. (1996). The phosphorylation of eukaryotic initiation factor 2 and its role in the regulation of translation during viral infection. In: Resnekov, O., von Gabain, A. (eds) Post-transcriptional Control of Gene Expression. NATO ASI Series, vol 97. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-60929-9_15
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DOI: https://doi.org/10.1007/978-3-642-60929-9_15
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