• 1
    Kleijn, M., Scheper, G.C., Voorma, H.O. & Thomas, A.A.M. (1998) Regulation of translation initiation factors by signal transduction. Eur. J. Biochem. 253, 531544.
  • 2
    Rhoads, R.E. (1999) Signal transduction pathways that regulate eukaryotic protein synthesis. J. Biol. Chem. 274, 3033730340.
  • 3
    Gingras, A.-C., Raught, B. & Sonenberg, N. (1999) eIF4 Translation Factors: Effectors of mRNA recruitment to ribosomes and regulators of translation. Annu. Rev. Biochem. 68, 913963.
  • 4
    Flynn, A. & Proud, C.G. (1996) The role of eIF4 in cell proliferation. Cancer Surveys 27, 293310.
  • 5
    Flynn, A. & Proud, C.G. (1995) Serine 209, not serine 53, is the major site of phosphorylation in initiation factor eIF-4E in serum-treated Chinese hamster ovary cells. J. Biol. Chem. 270, 2168421688.
  • 6
    Joshi, B., Cai, A.L., Keiper, B.D., Minich, W.B., Mendez, R., Beach, C.M., Stolarski, R., Darzynkiewicz, E. & Rhoads, R.E. (1995) Phosphorylation of eukaryotic protein synthesis initiation factor eIF4E at serine 209. J. Biol. Chem. 270, 1459714603.
  • 7
    Lawrence, J.C. & Abraham, R.T. (1997) PHAS/4E-BPs as regulators of mRNA translation and cell proliferation. Trends Biochem. Sci. 22, 345349.
  • 8
    Raught, B., Gingras, A.-C. & Sonenberg, N. (2000) Regulation of ribosome recruitment in eukaryotes. In Translational Control of Gene Expression (Sonenberg, N., Hershey, J.W.B. & Mathews, M.B., eds), pp. 245293. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
  • 9
    Sierra, J.M. & Zapata, J.M. (1994) Translational regulation of the heat shock response. Mol. Biol. Report 19, 211220.
  • 10
    Duncan, R.F. (1996) Translational control during heat shock. In Translational Control. (Hershey, J.W.B., Mathews, M.B. & Sonenberg, N., eds), pp. 271294. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
  • 11
    Rhoads, R.E. & Lamphear, B.J. (1995) Cap-independent translation of heat shock messenger RNAs. Curr. Topics Microbiol. Immunol. 203, 131153.
  • 12
    Sarnow, P. (1989) Translation of glucose-regulated protein-78-immunoglobulin heavy chain binding protein mRNA is increased in poliovirus infected cells at a time when cap-dependent translation of cellular mRNAs is inhibited. Proc. Natl Acad. Sci. USA 86, 57955799.
  • 13
    Pause, A., Belsham, G.J., Gingras, A.-C., Donzé, O., Lin, T.A., Lawrence, J.C. & Sonenberg, N. (1994) Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5′-cap function. Nature 371, 762767.
  • 14
    Lin, T.-A., Kong, X., Haystead, T.A.J., Pause, A., Belsham, G.J., Sonenberg, N. & Lawrence, J.C. (1994) PHAS-I as a link between mitogen-activated protein kinase and translation initiation. Science 266, 653656.
  • 15
    Beretta, L., Gingras, A.-C., Svitkin, Y.V., Hall, M.N. & Sonenberg, N. (1996) Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent translation. EMBO J. 15, 658664.
  • 16
    Haghighat, A., Mader, S., Pause, A. & Sonenberg, N. (1995) Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E. EMBO J. 14, 57015709.
  • 17
    Mader, S., Lee, H., Pause, A. & Sonenberg, N. (1995) The translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4gamma and the translational repressors 4E-binding proteins. Mol. Cell. Biol. 15, 49904997.
  • 18
    Lin, T.A. & Lawrence, J.C. (1996) Control of the translational regulators PHAS-I and PHAS-II by insulin and cAMP in 3T3-L1 adipocytes. J. Biol. Chem. 271, 3019930204.
  • 19
    Von Manteuffel, S.R., Dennis, P.B., Pullen, N., Gingras, A.-C., Sonenberg, N. & Thomas, G. (1997) The insulin-induced signalling pathway leading to S6 and initiation factor 4E binding protein 1 phosphorylation bifurcates at a rapamycin-sensitive point upstream of p70S6k. Mol. Cell. Biol. 17, 54265436.
  • 20
    Avruch, J., Nelham, C., Wang, Q., Hara, K. & Yonezawa, K. (2001) The p70, S6 kinase integrates nutrient and growth signals to control translational capacity. Prog. Mol. Subcell. Biol. 26, 115154.
  • 21
    Meyuhas, O. & Hornstein, E. (2000) Translational control of TOP mRNAs. In Translational Control of Gene Expression (Sonenberg, N., Hershey, J.W.B. & Mathews, M.B., eds), pp. 671693. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
  • 22
    Fumagalli, S. & Thomas, G. (2000) S6 phosphorylation and signal transduction.
  • 23
    Ryazanov, A.G., Rudkin, B.B. & Spirin, A.S. (1991) Regulation of protein synthesis at the elongation stage. New insights into the control of gene expression in eukaryotes. FEBS Lett. 285, 170175.
  • 24
    Proud, C.G. (2000) Control of the elongation phase of protein synthesis. In Translational Control of Gene Expression (Sonenberg, N., Hershey, J.W.B. & Mathews, M.B., eds), pp. 719739. Cold Spring. Harbor Laboratory Press, Cold Spring Harbor, NY.
  • 25
    Carlberg, U., Nilsson, A. & Nygard, O. (1990) Functional properties of phosphorylated elongation factor 2. Eur. J. Biochem. 191, 639645.
  • 26
    Redpath, N.T., Foulstone, E.J. & Proud, C.G. (1996) Regulation of translation elongation factor-2 by insulin via a rapamycin-sensitive signalling pathway. EMBO J. 15, 22912297.
  • 27
    Diggle, T.A., Redpath, N.T., Heesom, K.J. & Denton, R.M. (1998) Regulation of protein synthesis elongation factor-2 kinase by cAMP in adipocytes. Biochem. J. 336, 525529.
  • 28
    Wang, X., Li, W., Williams, M., Terada, N., Alessi, D.R. & Proud, C.G. (2001) Regulation of elongation factor 2 kinase by p90RSK1 and p70, S6 kinase. EMBO J. 20, 43704379.
  • 29
    Hinnebusch, A.G. (2000) Mechanism and regulation of methionyl-tRNA binding to ribosomes. In Translational Control of Gene Expression. (Sonenberg, N., Hershey, J.W.B. & Mathews, M.B., eds), pp. 184243. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
  • 30
    Webb, B.L.J. & Proud, C.G. (1998) Eukaryotic initiation factor 2B (eIF2B). Int. J. Biochem. Cell Biol. 29, 11271131.
  • 31
    Clemens, M.J. (1996) Protein kinases that phosphorylate eIF2 and eIF2B, and their role in eukaryotic cell translational control. In Translational Control. (Hershey, J.W.B., Mathews, M.B. & Sonenberg, N., eds), pp. 139172. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, USA
  • 32
    Colthurst, D.R., Campbell, D.G. & Proud, C.G. (1987) Structure and regulation of eukaryotic initiation factor eIF-2. Sequence of the site in the alpha subunit phosphorylated by the haem-controlled repressor and by the double-stranded RNA- activated inhibitor. Eur. J. Biochem. 166, 357363.
  • 33
    Flynn, A. & Proud, C.G. (1996) Insulin and phorbol ester stimulate eIF-4E phosphorylation by distinct pathways in Chinese hamster ovary cells overexpressing the insulin receptor. Eur. J. Biochem. 236, 4047.
  • 34
    Diggle, T.A., Moule, S.K., Avison, M.B., Flynn, A., Foulstone, E.J., Proud, C.G. & Denton, R.M. (1996) Both rapamycin-sensitive and -insensitive pathways are involved in the phosphorylation of the initiation factor 4E binding protein (4E-BP1) in response to insulin in rat epididymal fat cells. Biochem. J. 316, 447453.
  • 35
    Li, W., Belsham, G.J. & Proud, C.G. (2001) Eukaryotic initiation factors 4A (eIF4A) and 4G (eIF4G) mutually interact in a 1: 1 ratio in vivo. J. Biol. Chem. 276, 2911129115.
  • 36
    McLeod, L.E., Wang, L. & Proud, C.G. (2001) β-Adrenergic agonists increase phosphorylation of elongation factor 2 in cardiomyocytes without eliciting calcium-independent eEF2 kinase activity. FEBS Lett. 489, 225228.
  • 37
    Redpath, N.T. (1992) High-resolution one-dimensional polyacrylamide gel isoelectric focusing of various forms of elongation factor-2. Anal Biochem. 202, 340343.
  • 38
    Dickens, M., Chin, J.E., Roth, R.A., Ellis, L., Denton, R.M. & Tavaré, J.M. (1992) Characterization of insulin-stimulated protein serine/threonine kinases in CHO cells expressing human insulin receptors with point and deletion mutations. Biochem. J. 287, 201209.
  • 39
    Flynn, A. & Proud, C.G. (1996) Insulin stimulation of the phosphorylation of initiation factor 4E is mediated by the MAP kinase pathway. FEBS Lett. 389, 162166.
  • 40
    Oldfield, S., Jones, B.L., Tanton, D. & Proud, C.G. (1994) Use of monoclonal-antibodies to study the structure and function of eukaryotic protein synthesis initiation-factor-2B. Eur. J. Biochem. 221, 399410.
  • 41
    Welsh, G.I. & Proud, C.G. (1992) Regulation of protein synthesis in Swiss 3T3 fibroblasts. Rapid activation of the guanine-nucleotide-exchange factor by insulin and growth factors. Biochem. J. 284, 1923.
  • 42
    Moule, S.K., Edgell, N.J., Welsh, G.I., Diggle, T.A., Foulstone, E.J., Heesom, K.J., Proud, C.G. & Denton, R.M. (1995) Multiple signalling pathways involved in the stimulation of fatty acid and glycogen synthesis by insulin in rat epididymal fat pads. Biochem. J. 311, 595601.
  • 43
    Vries, R.G.J., Flynn, A., Patel, J.C., Wang, X., Denton, R.M. & Proud, C.G. (1997) Heat shock increases the association of binding protein-1 with initiation factor 4E. J. Biol. Chem. 272, 3277932784.
  • 44
    Cano, E., Hazzalin, C.A. & Mahadevan, L.C. (1994) Anisomycin-activated protein kinases p45 and p55 but not mitogen-activated protein kinases ERK-1 and – 2 are implicated in the induction of c-fos and c-jun. Mol. Cell. Biol. 14, 73527362.
  • 45
    Zinck, R., Cahill, M.A., Kracht, M., Sachsenmaier, C., Hipskind, R.A. & Nordheim, A. (1995) Protein synthesis inhibitors reveal differential regulation of mitogen-activated protein kinase and stress-activated protein kinase pathways that converge on Elk-1. Mol. Cell. Biol. 15, 49304938.
  • 46
    Bogoyevitch, M.A., Ketterman, A.J. & Sugden, P.H. (1995) Cellular stresses differentially activate c-Jun N-terminal protein kinases and extracellular ligand regulated protein kinases in cultured ventricular myocytes. J. Biol. Chem. 270, 2971029717.
  • 47
    Yang, D.-Q. & Kastan, M.B. (2000) Participation of ATM in insulin signalling through phosphorylation of eIF-4E-binding protein 1. Nat. Cell Biol. 2, 893898.
  • 48
    Heesom, K.J., Avison, M.B., Diggle, T.A. & Denton, R.M. (1998) Insulin-stimulated kinase from rat fat cells that phosphorylates initiation factor 4E-binding protein 1 on the rapamycin-insensitive site (serine-111). Biochem. J. 336, 3948.
  • 49
    Mothe-Satney, I., Yang, D., Fadden, P., Haystead, T.A. & Lawrence, J.C. (2000) Multiple mechanisms control phosphorylation of PHAS-I in five (S/T)P sites that govern translational repression. Mol. Cell. Biol. 20, 35583567.
  • 50
    Gingras, A.-C., Raught, B., Gygi, S.P., Niedzwiecka, A., Miron, M., Burley, S.K., Polakiewicz, R.D., Wyslouch-Cieszynska, A., Aebersold, R. & Sonenberg, N. (2001) Hierarchical phosphorylation of the translation inhibitor 4E-BP1. Genes Dev. 15, 28522864.
  • 51
    Wang, X., Campbell, L.E., Miller, C.M. & Proud, C.G. (1998) Amino acid availability regulates p70, S6 kinase and multiple translation factors. Biochem. J. 334, 261267.
  • 52
    Campbell, L.E., Wang, X. & Proud, C.G. (1999) Nutrients differentially modulate multiple translation factors and their control by insulin. Biochem. J. 344, 433441.DOI: 10.1042/0264-6021:3440433
  • 53
    Scheper, G.C., van Wijk, R. & Thomas, A.A.M. (2001) Regulation of the activity of eukaryotic initiation factors in stressed cells. Prog. Mol. Subcell. Biol. 27, 3956.
  • 54
    Wang, X. & Proud, C.G. (1997) p70, S6 kinase is activated by sodium arsenite in adult rat cardiomyocytes: roles for phosphatidylinositol 3-kinase and p38 MAP kinase. Biochem. Biophys. Res. Commun 238, 207212.
  • 55
    Ryazanov, A.G. & Spirin, A.S. (1990) Phosphorylation of elongation factor 2: a key mechanism regulating gene expression in vertebrates. New Biol. 2, 843850.
  • 56
    Cuenda, A., Rouse, J., Doza, Y.N., Meier, R., Cohen, P., Gallagher, T.F., Young, P.R. & Lee, J.C. (1995) SB-203580 is a specific inhibitor of a MAP kinase homolog which is activated by cellular stresses and interleukin-1. FEBS Lett. 364, 229233.
  • 57
    Knebel, A., Morrice, N. & Cohen, P. (2001) A novel method to identify protein kinase substrates: eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta. EMBO J. 20, 43604369.
  • 58
    Parrott, L.A. & Templeton, D.J. (1999) Osmotic stress inhibits p70/85, S6 kinase through activation of a protein phosphatase. J. Biol. Chem. 274, 2473124736.
  • 59
    Kyriakis, J.M. & Avruch, J. (2001) Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol. Rev. 81, 807869.
  • 60
    Scheper, G.C., Thomas, A.A.M. & van Wijk, R. (1998) Inactivation of eukaryotic initiation factor 2B in vitro by heat shock. Biochem. J. 334, 463467.
  • 61
    Wang, X., Flynn, A., Waskiewicz, A.J., Webb, B.L.J., Vries, R.G., Baines, I.A., Cooper, J. & Proud, C.G. (1998) The phosphorylation of eukaryotic initiation factor eIF4E in response to phorbol esters, cell stresses and cytokines is mediated by distinct MAP kinase pathways. J. Biol. Chem. 273, 93739377.
  • 62
    Kedersha, N., Cho, M.R., Li, W., Yacono, P.W., Chen, S., Gilks, N., Golan, D.E. & Anderson, P. (2000) Dynamic shuttling of TIA-1 accompanies the recruitment of mRNA to mammalian stress granules. J. Cell Biol. 151, 12571268.
  • 63
    Kedersha, N.L., Gupta, M., Li, W., Miller, I. & Anderson. P. (1999) RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2 alpha to the assembly of mammalian stress granules. J. Cell Biol. 1999, 14311441.
  • 64
    Novoa, I. & Carrasco, L. (1999) Cleavage of eukaryotic translation initiation factor 4G by exogenously added hybrid proteins containing poliovirus 2Apro in HeLa cells: effects on gene expression. Mol. Cell. Biol. 19, 24452454.
  • 65
    Pestova, T.V., Kolupaeva, V.G., Lomakin, I.B., Pilipenko, E.V., Shatsky, I.N., Agol, V.I. & Hellen, C.U. (2001) Molecular mechanisms of translation initiation in eukaryotes. Proc. Natl Acad. Sci. USA 98, 70297036.
  • 66
    Macejak, D.G. & Sarnow, P. (1990) Translational regulation of the immunoglobulin heavy-chain binding protein mRNA. Enzyme 44, 310319.
  • 67
    Joshi-Barve, S., De Benedetti, A. & Rhoads, R.E. (1992) Preferential translation of heat shock mRNAs in HeLa cells deficient in protein synthesis initiation factors eIF-4E and eIF- 4 gamma. J. Biol. Chem. 267, 2103821043.
  • 68
    Vivinus, S., Baulande, S., van Zanten, M., Campbell, F., Topley, P., Ellis, J.H., Dessen, P. & Coste, H. (2001) An element within the 5′ untranslated region of human Hsp70 mRNA which acts as a general enhancer of mRNA translation. Eur. J. Biochem. 268, 19081917.