Functional Plant Biology Functional Plant Biology Society
Plant function and evolutionary biology
REVIEW

A critical review of translation initiation factor eIF2α kinases in plants – regulating protein synthesis during stress

Tracey M. Immanuel A B , David R. Greenwood A B and Robin M. MacDiarmid A B C
+ Author Affiliations
- Author Affiliations

A The New Zealand Institute for Plant & Food Research Limited, Private Bag 92169, Auckland, 1142, New Zealand.

B School of Biological Sciences, the University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland, 1142, New Zealand.

C Corresponding author. Email: robin.macdiarmid@plantandfood.co.nz

Functional Plant Biology 39(9) 717-735 https://doi.org/10.1071/FP12116
Submitted: 16 April 2012  Accepted: 10 July 2012   Published: 20 August 2012

Abstract

Eukaryotic cells must cope with environmental stress. One type of general stress response is the downregulation of protein synthesis in order to conserve cellular resources. Protein synthesis is mainly regulated at the level of mRNA translation initiation and when the α subunit of eukaryotic translation initiation factor 2 (eIF2) is phosphorylated, protein synthesis is downregulated. Although eIF2 has the same translation initiation function in all eukaryotes, it is not known whether plants downregulate protein synthesis via eIF2α phosphorylation. Similarly, although there is evidence that plants possess eIF2α kinases, it is not known whether they operate in a similar manner to the well characterised mammalian and yeast eIF2α kinases. Two types of eIF2α kinases have been reported in plants, yet the full understanding of the plant eIF2α phosphorylation mechanism is still lacking. Here we review the current knowledge of the eIF2α phosphorylation mechanism within plants and discuss plant eIF2α, plant eIF2α kinase GCN2 and the data supporting and contradicting the hypothesis that a functional orthologue for the eIF2α kinase PKR, is present and functional in plants.

Additional keywords: Arabidopsis, GCN2, phosphorylation, PKR, plant, translation initiation.


References

Aparicio F, Aparicio-Sanchis R, Gadea J, Sanchez-Navarro JA, Pallas V, Murguia JR (2011) A plant virus movement protein regulates the Gcn2p kinase in budding yeast. PLoS ONE 6, e27409
A plant virus movement protein regulates the Gcn2p kinase in budding yeast.CrossRef | 1:CAS:528:DC%2BC3MXhsFGjs7zE&md5=c98e5a67256f117f75090726950f9cdfCAS |

Berlanga JJ, Santoyo J, de Haro C (1999) Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2 alpha kinase. European Journal of Biochemistry 265, 754–762.
Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2 alpha kinase.CrossRef | 1:CAS:528:DyaK1MXmslGlur0%3D&md5=8cd2ba05ad7630c7bb1937b2ae4e8428CAS |

Berlanga JJ, Ventoso I, Harding HP, Deng J, Ron D, Sonenberg N, Carrasco L, de Haro C (2006) Antiviral effect of the mammalian translation initiation factor 2 alpha kinase GCN2 against RNA viruses. EMBO Journal 25, 1730–1740.
Antiviral effect of the mammalian translation initiation factor 2 alpha kinase GCN2 against RNA viruses.CrossRef | 1:CAS:528:DC%2BD28XjsFaktb0%3D&md5=119535a59751d9ff215cea2f1c13fb65CAS |

Bilgin DD, Liu Y, Schiff M, Dinesh-Kumar SP (2003) P58(IPK), a plant ortholog of double-stranded RNA-dependent protein kinase PKR inhibitor, functions in viral pathogenesis. Developmental Cell 4, 651–661.
P58(IPK), a plant ortholog of double-stranded RNA-dependent protein kinase PKR inhibitor, functions in viral pathogenesis.CrossRef | 1:CAS:528:DC%2BD3sXjvFGltro%3D&md5=c05d4046abf466669bc6ce0148798a29CAS |

Browning KS (2004) Plant translation initiation factors: it is not easy to be green. Biochemical Society Transactions 32, 589–591.
Plant translation initiation factors: it is not easy to be green.CrossRef | 1:CAS:528:DC%2BD2cXmtFGjsb8%3D&md5=27354c936e06e48e548a5338ccd7fcdcCAS |

Browning KS, Yan TFJ, Lauer SJ, Aquino LA, Tao M, Ravel JM (1985) Phosphorylation of wheat germ initiation factors and ribosomal proteins. Plant Physiology 77, 370–373.
Phosphorylation of wheat germ initiation factors and ribosomal proteins.CrossRef | 1:CAS:528:DyaL2MXhs1ars7s%3D&md5=75b21ad506fb96b218591cc8daceb3d3CAS |

Byrne EH, Prosser I, Muttucumaru N, Curtis TY, Wingler A, Powers S, Halford NG (2012) Overexpression of GCN2-type protein kinase in wheat has profound effects on free amino acid concentration and gene expression. Plant Biotechnology Journal 10, 328–340.
Overexpression of GCN2-type protein kinase in wheat has profound effects on free amino acid concentration and gene expression.CrossRef | 1:CAS:528:DC%2BC38Xmt1ymt7w%3D&md5=d9c62862842d2da76049a2e4fe8d7f3fCAS |

Chang LY, Yang WY, Browning K, Roth D (1999) Specific in vitro phosphorylation of plant eIF2 alpha by eukaryotic eIF2 alpha kinases. Plant Molecular Biology 41, 363–370.
Specific in vitro phosphorylation of plant eIF2 alpha by eukaryotic eIF2 alpha kinases.CrossRef | 1:CAS:528:DyaK1MXnvVClt7Y%3D&md5=75f8e49b09a1633263b4cfce9aa89667CAS |

Chang LY, Yang WY, Roth D (2000) Functional complementation by wheat elF2 alpha in the yeast GCN2-mediated pathway. Biochemical and Biophysical Research Communications 279, 468–474.
Functional complementation by wheat elF2 alpha in the yeast GCN2-mediated pathway.CrossRef | 1:CAS:528:DC%2BD3cXovVCntLw%3D&md5=9ab511069039ef728c8107ceaee51c91CAS |

Chen JJ, London IM (1995) Regulation of protein-synthesis by heme-regulated Eif-2-alpha kinase. Trends in Biochemical Sciences 20, 105–108.
Regulation of protein-synthesis by heme-regulated Eif-2-alpha kinase.CrossRef | 1:CAS:528:DyaK2MXktlClsr4%3D&md5=31f0d516039e863ea82954860ba30fbeCAS |

Churbanov A, Rogozin IB, Babenko VN, Ali H, Koonin EV (2005) Evolutionary conservation suggests a regulatory function of AUG triplets in 5′-UTRs of eukaryotic genes. Nucleic Acids Research 33, 5512–5520.
Evolutionary conservation suggests a regulatory function of AUG triplets in 5′-UTRs of eukaryotic genes.CrossRef | 1:CAS:528:DC%2BD2MXhtFWltr3J&md5=f384d613c7d3e67ef14eac4f181a5afbCAS |

Crum CJ, Hu J, Hiddinga HJ, Roth DA (1988) Tobacco mosaic-virus infection stimulates the phosphorylation of a plant protein associated with double-stranded RNA-dependent protein-kinase activity. Journal of Biological Chemistry 263, 13440–13443.

Deng J, Harding HP, Raught B, Gingras AC, Berlanga JJ, Scheuner D, Kaufman RJ, Ron D, Sonenberg N (2002) Activation of GCN2 in UV-irradiated cells inhibits translation. Current Biology 12, 1279–1286.
Activation of GCN2 in UV-irradiated cells inhibits translation.CrossRef | 1:CAS:528:DC%2BD38XmtlKhu7c%3D&md5=25b910d69695a1c042ee2a04ea456bc8CAS |

Deprost D, Yao L, Sormani R, Moreau M, Leterreux G, Nicolai M, Bedu M, Robaglia C, Meyer C (2007) The Arabidopsis TOR kinase links plant growth, yield, stress resistance and mRNA translation. EMBO Reports 8, 864–870.
The Arabidopsis TOR kinase links plant growth, yield, stress resistance and mRNA translation.CrossRef | 1:CAS:528:DC%2BD2sXpvFWks7o%3D&md5=69f8628269120d5cd81a27ed3d41c528CAS |

Dever TE, Feng L, Wek RC, Cigan AM, Donahue TF, Hinnebusch AG (1992) Phosphorylation of initiation factor 2 alpha by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast. Cell 68, 585–596.
Phosphorylation of initiation factor 2 alpha by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast.CrossRef | 1:CAS:528:DyaK38XhsVOrtrw%3D&md5=2bba749df229e72b25398fd05085a8e8CAS |

Dever TE, Yang WM, Astrom S, Bystrom AS, Hinnebusch AG (1995) Modulation of Trna(I)(Met), Eif-2, and Eif-2b expression shows that Gcn4 translation is inversely coupled to the level of Eif-2-Center-Dot-Gtp-Center-Dot-Met-Trna(I)(Met) ternary complexes. Molecular and Cellular Biology 15, 6351–6363.

Dey M, Trieselmann B, Locke EG, Lu J, Cao C, Dar AC, Krishnamoorthy T, Dong J, Sicheri F, Dever TE (2005) PKR and GCN2 kinases and guanine nucleotide exchange factor eukaryotic translation initiation factor 2B (eIF2B) recognize overlapping surfaces on eIF2 alpha. Molecular and Cellular Biology 25, 3063–3075.
PKR and GCN2 kinases and guanine nucleotide exchange factor eukaryotic translation initiation factor 2B (eIF2B) recognize overlapping surfaces on eIF2 alpha.CrossRef | 1:CAS:528:DC%2BD2MXjt12qu7k%3D&md5=7b8d2262e894b504638dc51cb4830301CAS |

Dong JS, Qiu HF, Garcia-Barrio M, Anderson J, Hinnebusch AG (2000) Uncharged tRNA activates GCN2 by displacing the protein kinase moiety from a bipartite tRNA-Binding domain. Molecular Cell 6, 269–279.
Uncharged tRNA activates GCN2 by displacing the protein kinase moiety from a bipartite tRNA-Binding domain.CrossRef | 1:CAS:528:DC%2BD3cXmsFWmsb4%3D&md5=feb27ab3e4ce94b0c5fd6821ba7e6da3CAS |

Evans RK, Haley BE, Roth DA (1985) Photoaffinity-labeling of a viral induced protein from tobacco – characterization of nucleotide-binding properties. The Journal of Biological Chemistry 260, 7800–7804.

Gallie DR, Le H, Caldwell C, Tanguay RL, Hoang NX, Browning KS (1997) The phosphorylation state of translation initiation factors is regulated developmentally and following heat shock in wheat. The Journal of Biological Chemistry 272, 1046–1053.
The phosphorylation state of translation initiation factors is regulated developmentally and following heat shock in wheat.CrossRef | 1:CAS:528:DyaK2sXmtFGlsw%3D%3D&md5=98f9dc7104b86c1c3918e6be03fc8bacCAS |

Gil J, Esteban M, Roth D (2000) In vivo regulation of protein synthesis by phosphorylation of the alpha subunit of wheat eukaryotic initiation factor 2. Biochemistry 39, 7521–7530.
In vivo regulation of protein synthesis by phosphorylation of the alpha subunit of wheat eukaryotic initiation factor 2.CrossRef | 1:CAS:528:DC%2BD3cXjs1KnsbY%3D&md5=455ef0ba27132e71c5ab1809a54f5aedCAS |

Guyer D, Patton D, Ward E (1995) Evidence for cross-pathway regulation of metabolic gene-expression in plants. Proceedings of the National Academy of Sciences of the United States of America 92, 4997–5000.
Evidence for cross-pathway regulation of metabolic gene-expression in plants.CrossRef | 1:CAS:528:DyaK2MXlvFyitrc%3D&md5=26e8a78208e7a6e3a51f9cf60f5ab10aCAS |

Harding HP, Zhang YH, Ron D (1999) Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase. Nature 397, 271–274.
Protein translation and folding are coupled by an endoplasmic-reticulum-resident kinase.CrossRef | 1:CAS:528:DyaK1MXpvVGrtA%3D%3D&md5=082e5d4a3e3378702294775dda103e78CAS |

Harding HP, Novoa I, Zhang YH, Zeng HQ, Wek R, Schapira M, Ron D (2000) Regulated translation initiation controls stress-induced gene expression in mammalian cells. Molecular Cell 6, 1099–1108.
Regulated translation initiation controls stress-induced gene expression in mammalian cells.CrossRef | 1:CAS:528:DC%2BD3cXosV2mtrs%3D&md5=bd489d170adeaa333b1c2927336d8759CAS |

Harding HP, Zhang YH, Zeng H, Novoa I, Lu PD, Calfon M, Sadri N, Yun C, Popko B, Paules R, Stojdl DF, Bell JC, Hettmann T, Leiden JM, Ron D (2003) An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Molecular Cell 11, 619–633.
An integrated stress response regulates amino acid metabolism and resistance to oxidative stress.CrossRef | 1:CAS:528:DC%2BD3sXjtVWkt74%3D&md5=cc61c809ae0cd541525a3e0ec5030977CAS |

Hey SJ, Byrne E, Halford NG (2010) The interface between metabolic and stress signalling. Annals of Botany 105, 197–203.
The interface between metabolic and stress signalling.CrossRef | 1:CAS:528:DC%2BC3cXhslKksbk%3D&md5=ba6b881bbf06dc1a8e37ad9d15284e9aCAS |

Hiddinga HJ, Crum CJ, Hu J, Roth DA (1988) Viroid-induced phosphorylation of a host protein related to a Dsrna-dependent protein-kinase. Science 241, 451–453.
Viroid-induced phosphorylation of a host protein related to a Dsrna-dependent protein-kinase.CrossRef | 1:CAS:528:DyaL1cXlt1KjsLs%3D&md5=4a5990d53a6beaa6528d0706f364aa28CAS |

Hinnebusch AG (2005) Translational regulation of GCN4 and the general amino acid control of yeast. Annual Review of Microbiology 59, 407–450.
Translational regulation of GCN4 and the general amino acid control of yeast.CrossRef | 1:CAS:528:DC%2BD2MXht1ShsL7N&md5=019a413473e915f7923503257fb573dfCAS |

Hu J, Roth D (1991) Temporal regulation of tobacco mosaic virus-induced phosphorylation of a host encoded protein. Biochemical and Biophysical Research Communications 179, 229–235.
Temporal regulation of tobacco mosaic virus-induced phosphorylation of a host encoded protein.CrossRef | 1:CAS:528:DyaK3MXlsl2mtbo%3D&md5=211105095fb99bdfc92fe7bffe7110b0CAS |

Hu CY, Zhang YB, Huang GP, Zhang QY, Gui HF (2004) Molecular cloning and characterisation of a fish PKR-like gene from cultured CAB cells induced by UV-inactivated virus. Fish & Shellfish Immunology 17, 353–366.
Molecular cloning and characterisation of a fish PKR-like gene from cultured CAB cells induced by UV-inactivated virus.CrossRef | 1:CAS:528:DC%2BD2cXmslOgsb0%3D&md5=d07b8dfb085f165372418efb7f5948dbCAS |

Kamauchi S, Nakatani H, Nakano C, Urade R (2005) Gene expression in response to endoplasmic reticulum stress in Arabidopsis thaliana. The FEBS Journal 272, 3461–3476.
Gene expression in response to endoplasmic reticulum stress in Arabidopsis thaliana.CrossRef | 1:CAS:528:DC%2BD2MXmtFKrurY%3D&md5=47a26ee2cf31de0ba67b6ed0d5cf57a0CAS |

Kawagishi-Kobayashi M, Silverman JB, Ung TL, Dever TE (1997) Regulation of the protein kinase PKR by the vaccinia virus pseudosubstrate inhibitor K3L is dependent on residues conserved between the K3L protein and the PKR substrate eIF2alpha. Molecular and Cellular Biology 17, 4146–4158.

Kawaguchi R, Bailey-Serres J (2005) mRNA sequence features that contribute to translational regulation in Arabidopsis. Nucleic Acids Research 33, 955–965.
mRNA sequence features that contribute to translational regulation in Arabidopsis.CrossRef | 1:CAS:528:DC%2BD2MXitVyqu78%3D&md5=2c34170a5ac09c6beabf01273ff3bb3cCAS |

Koumenis C, Naczki C, Koritzinsky M, Rastani S, Diehl A, Sonenberg N, Koromilas A, Wouters BG (2002) Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2 alpha. Molecular and Cellular Biology 22, 7405–7416.
Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2 alpha.CrossRef | 1:CAS:528:DC%2BD38XotVKhs7k%3D&md5=064cd246ed65c314ac9144506ccf899cCAS |

Krishna VM, Janaki N, Ramaiah KVA (1997) Wheat germ initiation factor 2 (WG center dot eIF2) decreases the inhibition in protein synthesis and eIF2B activity of reticulocyte lysates mediated by eIF2 alpha phosphorylation. Archives of Biochemistry and Biophysics 346, 28–36.
Wheat germ initiation factor 2 (WG center dot eIF2) decreases the inhibition in protein synthesis and eIF2B activity of reticulocyte lysates mediated by eIF2 alpha phosphorylation.CrossRef | 1:CAS:528:DyaK2sXmsVajsL0%3D&md5=9c0ae88fe87b4b1002ad5040f2380b99CAS |

Krishnamoorthy T, Pavitt GD, Zhang F, Dever TE, Hinnebusch AG (2001) Tight binding of the phosphorylated alpha subunit of initiation factor 2 (eIF2 alpha) to the regulatory subunits of guanine nucleotide exchange factor eIF2B is required for inhibition of translation initiation. Molecular and Cellular Biology 21, 5018–5030.
Tight binding of the phosphorylated alpha subunit of initiation factor 2 (eIF2 alpha) to the regulatory subunits of guanine nucleotide exchange factor eIF2B is required for inhibition of translation initiation.CrossRef | 1:CAS:528:DC%2BD3MXlsVGit7c%3D&md5=fcba59dccd3a5f6fa140de605f14c821CAS |

Lageix S, Lanet E, Pouch-Pelissier MN, Espagnol MC, Robaglia C, Deragon JM, Pelissier T (2008) Arabidopsis eIF2 alpha kinase GCN2 is essential for growth in stress conditions and is activated by wounding. BMC Plant Biology 8, 134
Arabidopsis eIF2 alpha kinase GCN2 is essential for growth in stress conditions and is activated by wounding.CrossRef |

Lam HM, Chiao YA, Li MW, Yung YK, Ji S (2006) Putative nitrogen sensing systems in higher plants. Journal of Integrative Plant Biology 48, 873–888.
Putative nitrogen sensing systems in higher plants.CrossRef | 1:CAS:528:DC%2BD28XoslWksLw%3D&md5=1ec27b67b45c693dd6fd05745a59c806CAS |

Langland JO, Pettiford S, Jiang B, Jacobs BL (1994) Products of the Porcine Group C Rotavirus NSP3 gene bind specifically to double-stranded RNA and inhibit activation of the interferon-induced protein kinase PKR. Journal of Virology 68, 3821–3829.

Langland JO, Jin S, Jacobs BL, Roth DA (1995) Identification of a plant-encoded analog of PKR, the mammalian double-stranded RNA-Dependent protein-kinase. Plant Physiology 108, 1259–1267.
Identification of a plant-encoded analog of PKR, the mammalian double-stranded RNA-Dependent protein-kinase.CrossRef | 1:CAS:528:DyaK2MXmvFGmu7o%3D&md5=1a5be8fd2cbf7e35739b785abf241b0fCAS |

Langland JO, Langland LA, Browning KS, Roth DA (1996) Phosphorylation of plant eukaryotic initiation factor-2 by the plant-encoded double-stranded RNA-dependent protein kinase, pPKR, and inhibition of protein synthesis in vitro. The Journal of Biological Chemistry 271, 4539–4544.
Phosphorylation of plant eukaryotic initiation factor-2 by the plant-encoded double-stranded RNA-dependent protein kinase, pPKR, and inhibition of protein synthesis in vitro.CrossRef | 1:CAS:528:DyaK28XhtlSmurk%3D&md5=6dc610f1372302a97db7b786b4570a50CAS |

Langland JO, Langland L, Zeman C, Saha D, Roth DA (1997) Developmental regulation of a plant encoded inhibitor of eukaryotic initiation factor 2 alpha phosphorylation. The Plant Journal 12, 393–400.
Developmental regulation of a plant encoded inhibitor of eukaryotic initiation factor 2 alpha phosphorylation.CrossRef | 1:CAS:528:DyaK2sXmsVams7g%3D&md5=5f513d624fe1553df3d7770ba51b3e1aCAS |

Lim PO, Lee U, Ryu JS, Choi JK, Hovanessian A, Kim CS, Cho BH, Nam HG (2002) Multiple virus resistance in transgenic plants conferred by the human dsRNA-dependent protein kinase. Molecular Breeding 10, 11–18.
Multiple virus resistance in transgenic plants conferred by the human dsRNA-dependent protein kinase.CrossRef | 1:CAS:528:DC%2BD38Xnt1ahtrs%3D&md5=a7609d96423ab3d7a0e82320fb1a7da6CAS |

Manche L, Green SR, Schmedt C, Mathews MB (1992) Interactions between double-stranded-RNA regulators and the protein-kinase dai. Molecular and Cellular Biology 12, 5238–5248.

Mauri I, Maddaloni M, Lohmer S, Motto M, Salamini F, Thompson R, Martegani E (1993) Functional expression of the transcriptional activator Opaque-2 of Zea mays in transformed yeast. Molecular & General Genetics 241, 319–326.
Functional expression of the transcriptional activator Opaque-2 of Zea mays in transformed yeast.CrossRef | 1:CAS:528:DyaK2cXksFWhurw%3D&md5=245b0007514d6c8407a4ec0590ef636dCAS |

Mellor H, Proud CG (1991) A synthetic peptide substrate for initiation factor-Ii kinases. Biochemical and Biophysical Research Communications 178, 430–437.
A synthetic peptide substrate for initiation factor-Ii kinases.CrossRef | 1:CAS:528:DyaK3MXlslOqu70%3D&md5=b01b3993cb420312a7cdbfaf85dcc364CAS |

Preiss T, Hentze MW (2003) Starting the protein synthesis machine: eukaryotic translation initiation. BioEssays 25, 1201–1211.
Starting the protein synthesis machine: eukaryotic translation initiation.CrossRef | 1:CAS:528:DC%2BD2cXhtVOmtw%3D%3D&md5=7dfcbc2ab1efef547e18bf7133045754CAS |

Proud CG (2005) eIF2 and the control of cell physiology. Seminars in Cell & Developmental Biology 16, 3–12.
eIF2 and the control of cell physiology.CrossRef | 1:CAS:528:DC%2BD2MXkvFOhsQ%3D%3D&md5=2d2fa77bc4df1701d793c32dbde8c01cCAS |

Rahmani F, Hummel M, Schuurmans J, Wiese-Klinkenberg A, Smeekens S, Hanson J (2009) Sucrose control of translation mediated by an upstream open reading frame-encoded peptide. Plant Physiology 150, 1356–1367.
Sucrose control of translation mediated by an upstream open reading frame-encoded peptide.CrossRef | 1:CAS:528:DC%2BD1MXovFertbk%3D&md5=9c50d37d4accb79286b775feffcdad58CAS |

Ray MK, Datta B, Chakraborty A, Chattopadhyay A, Mezakeuthen S, Gupta NK (1992) The eukaryotic initiation factor-2-associated 67-Kda polypeptide (P67) plays a critical role in regulation of protein-synthesis initiation in animal-cells. Proceedings of the National Academy of Sciences of the United States of America 89, 539–543.
The eukaryotic initiation factor-2-associated 67-Kda polypeptide (P67) plays a critical role in regulation of protein-synthesis initiation in animal-cells.CrossRef | 1:CAS:528:DyaK38XotFSitw%3D%3D&md5=e291be43a20b810c72b27b25e7716af1CAS |

Reijnders L, Aalbers AMJ, Van Kammen A, Berns AJM (1975) The effect of double stranded cowpea mosaic viral RNA on protein synthesis. Biochimica et Biophysica Acta 390, 69–77.
The effect of double stranded cowpea mosaic viral RNA on protein synthesis.CrossRef | 1:CAS:528:DyaE2MXktValsro%3D&md5=2f7eebc20be8f21d60e507caa64824bbCAS |

Rolfes RJ, Hinnebusch AG (1993) Translation of the yeast transcriptional activator Gcn4 is stimulated by purine limitation – implications for activation of the protein-kinase Gcn2. Molecular and Cellular Biology 13, 5099–5111.

Roth DA, He X (1994) Viral-dependent phosphorylation of a dsRNA-dependent kinase. Progress in Molecular and Subcellular Biology 14, 28–47.
Viral-dependent phosphorylation of a dsRNA-dependent kinase.CrossRef | 1:CAS:528:DyaK2MXjsFyrtw%3D%3D&md5=1dfb40835242a06b0e7be3037ceb34edCAS |

Rothenburg S, Deigendesch N, Dittmar K, Koch-Nolte F, Haag F, Lowenhaupt K, Rich A (2005) A PKR-like eukaryotic initiation factor 2 alpha kinase from zebrafish contains Z-DNA binding domains instead of dsRNA binding domains. Proceedings of the National Academy of Sciences of the United States of America 102, 1602–1607.
A PKR-like eukaryotic initiation factor 2 alpha kinase from zebrafish contains Z-DNA binding domains instead of dsRNA binding domains.CrossRef | 1:CAS:528:DC%2BD2MXhs1Kltb8%3D&md5=0a45d910594e47e2dae765282b7131a7CAS |

Rothenburg S, Deigendesch N, Dey M, Dever TE, Tazi L (2008) Double-stranded RNA-activated protein kinase PKR of fishes and amphibians: varying the number of double-stranded RNA binding domains and lineage-specific duplications. BMC Biology 6, 12
Double-stranded RNA-activated protein kinase PKR of fishes and amphibians: varying the number of double-stranded RNA binding domains and lineage-specific duplications.CrossRef |

Rowlands AG, Panniers R, Henshaw EC (1988) The catalytic mechanism of guanine-nucleotide exchange factor action and competitive-inhibition by phosphorylated eukaryotic initiation factor-Ii. The Journal of Biological Chemistry 263, 5526–5533.

Sadler AJ, Williams BRG (2007) Structure and function of the protein kinase R. Interferon: The 50th Anniversary 316, 253–292.
Structure and function of the protein kinase R.CrossRef | 1:CAS:528:DC%2BD1cXhs12rtL0%3D&md5=ae1fb96e88db7659506cdfbbfc7d8b16CAS |

Shaikhin SM, Smailov SK, Lee AV, Kozhanov EV, Iskakov BK (1992) Interaction of wheat-germ translation initiation factor-Ii with Gdp and Gtp. Biochimie 74, 447–454.
Interaction of wheat-germ translation initiation factor-Ii with Gdp and Gtp.CrossRef | 1:CAS:528:DyaK38XlvVKrsLc%3D&md5=694a22ac5faaca2010a22538f586c564CAS |

Sormani R, Delannoy E, Lageix S, Bitton F, Lanet E, Saez-Vasquez J, Deragon JM, Renou JP, Robaglia C (2011) Sublethal cadmium intoxication in Arabidopsis thaliana impacts translation at multiple levels. Plant & Cell Physiology 52, 436–447.
Sublethal cadmium intoxication in Arabidopsis thaliana impacts translation at multiple levels.CrossRef | 1:CAS:528:DC%2BC3MXitVSrsL4%3D&md5=471a20e9305591ae8bcdcda1fbd434a1CAS |

Staschke KA, Dey S, Zaborske JM, Palam LR, McClintick JN, Pan T, Edenberg HJ, Wek RC (2010) Integration of general amino acid control and Target of Rapamycin (TOR) regulatory pathways in nitrogen assimilation in yeast. Journal of Biological Chemistry 285, 16893–16911.
Integration of general amino acid control and Target of Rapamycin (TOR) regulatory pathways in nitrogen assimilation in yeast.CrossRef | 1:CAS:528:DC%2BC3cXmtlygt70%3D&md5=7bd526698dcda2bde7e979edb130934bCAS |

Tan SL, Gale MJ, Katze MG (1998) Double-stranded RNA-independent dimerization of interferon-induced protein kinase PKR and inhibition of dimerization by the cellular P58(IPK) inhibitor. Molecular and Cellular Biology 18, 2431–2443.

Tournu H, Tripathi G, Bertram G, Macaskill S, Mavor A, Walker L, Odds FC, Gow NAR, Brown AJP (2005) Global role of the protein kinase Gcn2 in the human pathogen Candida albicans. Eukaryotic Cell 4, 1687–1696.
Global role of the protein kinase Gcn2 in the human pathogen Candida albicans.CrossRef | 1:CAS:528:DC%2BD2MXhtFCgt77F&md5=aaf9c3bf46d0c25eebad27fe6156af2dCAS |

Tripathi G, Wiltshire C, Macaskill S, Tournu H, Budge S, Brown AJP (2002) Gcn4 co-ordinates morphogenetic and metabolic responses to amino acid starvation in Candida albicans. EMBO Journal 21, 5448–5456.
Gcn4 co-ordinates morphogenetic and metabolic responses to amino acid starvation in Candida albicans.CrossRef | 1:CAS:528:DC%2BD38XnvF2qtL4%3D&md5=f1beaeedb722b91c9434aba7a14d8d1bCAS |

Vattem KM, Wek RC (2004) Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells. Proceedings of the National Academy of Sciences of the United States of America 101, 11269–11274.
Reinitiation involving upstream ORFs regulates ATF4 mRNA translation in mammalian cells.CrossRef | 1:CAS:528:DC%2BD2cXmvVKgt7o%3D&md5=9419cb58e95e06de30779fa0ab536b4dCAS |

Vincentz M, Bandeira-Kobarg C, Gauer L, Schlogl P, Leite A (2003) Evolutionary pattern of angiosperm bZIP factors homologous to the maize Opaque2 regulatory protein. Journal of Molecular Evolution 56, 105–116.
Evolutionary pattern of angiosperm bZIP factors homologous to the maize Opaque2 regulatory protein.CrossRef | 1:CAS:528:DC%2BD3sXpvFyjtw%3D%3D&md5=b6d9e6fe9c5fd23e9d9762fb24557b22CAS |

Wek SA, Zhu SH, Wek RC (1995) The histidyl-transfer-RNA synthetase-related sequence in the Eif-2-alpha protein-kinase Gcn2 interacts with transfer-RNA and is required for activation in response to starvation for different amino-acids. Molecular and Cellular Biology 15, 4497–4506.

Wiese A, Elzinga N, Wobbes B, Smeekens S (2004) A conserved upstream open sucrose-induced repression reading frame mediates of translation. The Plant Cell 16, 1717–1729.
A conserved upstream open sucrose-induced repression reading frame mediates of translation.CrossRef | 1:CAS:528:DC%2BD2cXmtFSqt7g%3D&md5=e4389356d327258d153adc351dbabf36CAS |

Williams BRG (1999) PKR; a sentinel kinase for cellular stress. Oncogene 18, 6112–6120.
PKR; a sentinel kinase for cellular stress.CrossRef | 1:CAS:528:DyaK1MXns1OqsrY%3D&md5=661cd930dc4206aed5d95ec34023a3c4CAS |

Yildirim-Ersoy F, Ridout CJ, Akkaya MS (2011) Detection of physically interacting proteins with the CC and NB-ARC domains of a putative yellow rust resistance protein, Yr10, in wheat. Journal of Plant Diseases and Protection 118, 119–126.

Zhan K, Narasimhan J, Wek RC (2004) Differential activation of eIF2 kinases in response to cellular stresses in Schizosaccharomyces pombe. Genetics 168, 1867–1875.
Differential activation of eIF2 kinases in response to cellular stresses in Schizosaccharomyces pombe.CrossRef | 1:CAS:528:DC%2BD2MXhtVOqu7s%3D&md5=662237d4e9be6f39383c48683748cd6bCAS |

Zhang YH, Dickinson JR, Paul MJ, Halford NG (2003) Molecular cloning of an Arabidopsis homologue of GCN2, a protein kinase involved in co-ordinated response to amino acid starvation. Planta 217, 668–675.
Molecular cloning of an Arabidopsis homologue of GCN2, a protein kinase involved in co-ordinated response to amino acid starvation.CrossRef | 1:CAS:528:DC%2BD3sXmtVWgsb0%3D&md5=d20a331ac929975db4a4b13bf071dbb8CAS |

Zhang YH, Wang YF, Kanyuka K, Parry MAJ, Powers SJ, Halford NG (2008) GCN2-dependent phosphorylation of eukaryotic translation initiation factor-2 alpha in Arabidopsis. Journal of Experimental Botany 59, 3131–3141.
GCN2-dependent phosphorylation of eukaryotic translation initiation factor-2 alpha in Arabidopsis.CrossRef | 1:CAS:528:DC%2BD1cXpslalsLo%3D&md5=9206a851f0e6aa46330c9d8c100dc288CAS |

Zhao JM, Williams CC, Last RL (1998) Induction of Arabidopsis tryptophan pathway enzymes and camalexin by amino acid starvation, oxidative stress, and an abiotic elicitor. The Plant Cell 10, 359–370.



Rent Article (via Deepdyve) Export Citation Cited By (6)