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Signaling Pathways for Translation pp 155–184Cite as

Regulation of Translation Initiation by Amino Acids in Eukaryotic Cells

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Part of the book series: Progress in Molecular and Subcellular Biology ((PMSB,volume 26))

Abstract

Deprivation of anyone of the essential amino acids results in a reduction in the rate of protein synthesis in a variety of cell types. Because amino acids serve as precursors in the synthesis of protein, it might logically be expected that lack of essential amino acids would restrict protein synthesis through a decrease in the rate of translation elongation. Such an expectation is based on the assumption that deprivation of a single essential amino acid, other than methionine, would cause a fall in the amount of the immediate precursor of protein synthesis, aminoacyl-tRNA, that in turn would result in a decline in the rate at which the growing peptide chain is elongated. However, instead of a restriction at the elongation step, the initiation phase of mRNA translation has been shown to be rate controlling under conditions of amino acid limitation. The goal of the present report is to review the mechanisms that are responsible for the inhibition of translation initiation caused by amino acid deprivation and examine possible sensors through which the deprivation is detected and transduced to the translational apparatus

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References

  • Abastado J-P, Miller PF, Jackson BM, Hinnebusch AG (1991) Suppression of ribosomal reinitiation at upstream open reading frames in amino acid-starved cells forms the basis for GCN4 translational control. Mol Cell Biol 11:486–496

    PubMed  CAS  Google Scholar 

  • Akimoto K, Nakaya M, Yamanaka T, Tanaka J, Matsuda S, Weng QP, Avruch J, Ohno S (1998) Atypical protein kinase Clambda binds and regulates p70 S6 kinase. Biochem J 335:417–424

    PubMed  CAS  Google Scholar 

  • Anthony JC, Anthony TG, Kimball SR, Vary TC, Jefferson LS (2000) Orally administered leucine stimulates protein synthesis in skeletal muscle of post-absorptive rats in association with increased eIF4F formation. J Nutr 130:139–145

    PubMed  CAS  Google Scholar 

  • Anthony JC, Yoshizawa F, Anthony TG, Vary TC, Jefferson LS, Kimball SR (2000) Leucine stimulates translation initiation in skeletal muscle of post-absorptive rats via a rapamycinsensitive pathway. J Nutr 130:2413–2419

    PubMed  CAS  Google Scholar 

  • Ashe MP, De Long SK, Sachs AB (2000) Glucose depletion rapidly inhibits translation initiation in yeast. Mol Biol Cell 11:833–848

    PubMed  CAS  Google Scholar 

  • Austin SA, Pollard JW, Jagus R, Clemens MJ (1986) Regulation of polypeptide chain initiation and activity of initiation factor eIF-2 in Chinese-hamster-ovary cell mutants containing temperature-sensitive aminoacyl-tRNA synthetases. Eur J Biochem 157:39–47

    PubMed  CAS  Google Scholar 

  • Barbet NC, Schneider U, Helliwell SB, Stansfield I, Tuite MF, Hall MN (1996) TOR controls translation initiation and early G1 progression in yeast. Mol Biol Cell 7:25–42

    PubMed  CAS  Google Scholar 

  • Bastians H, Ponstingl H (1996) The novel human protein serine/threonine phosphatase 6 is a functional homologue of budding yeast Sit4p and fission yeast ppel, which are involved in cell cycle regulation. J Cell Sci 109:2865–2874

    PubMed  CAS  Google Scholar 

  • Beck T, Schmidt A, Hall MN (1999) Starvation induces vacuolar targeting and degradation of the tryptophan permease in yeast. J Cell Biol 146:1227–1238

    PubMed  CAS  Google Scholar 

  • Begum N, Ragolia L (1996) cAMP counter-regulates insulin-mediated protein phosphatase-2A inactivation in rat skeletal muscle cells. J Biol Chem 271:31166–31171

    PubMed  CAS  Google Scholar 

  • Berlanga JJ, Santoyo J, de Haro C (1999) Characterization of a mammalian homolog of GCN2 eukaryotic initiation factor 2a kinase. Eur J Biochem 265:754–762

    PubMed  CAS  Google Scholar 

  • Brown EJ, Beal PA, Keith CT, Chen J, Shin TB, Schreiber SL (1995) Control of p70 S6 kinase by kinase activity of FRAP in vivo. Nature 377:441–446

    PubMed  CAS  Google Scholar 

  • Brunn GJ, Fadden P, Haystead TAJ, Lawrence JC (1997a) The mammalian target of rapamycin phosphorylates sites having a (Ser/Thr)-Pro motif and is activated by antibodies to a region near its COOH terminus. J Biol Chem 272:32547–32550

    PubMed  CAS  Google Scholar 

  • Brunn GJ, Hudson CC, Sekulic A, Williams JM, Hosoi H, Houghton PJ, Lawrence JC, Abraham RT (1997b) Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin. Science 277:99–101

    PubMed  CAS  Google Scholar 

  • Burnett PE, Barrow RK, Cohen NA, Snyder SH, Sabatini DM (1998) RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Proc Natl Acad Sci USA 95:1432–1437

    PubMed  CAS  Google Scholar 

  • Bushman JL, Asuru AI, Matts RL, Hinnebusch AG (1993a) Evidence that GCD6 and GCD7, translational regulators of GCN4, are subunits of the guanine nucleotide exchange factor for eIF-2 in Saccharomyces cerevisae. Mol Cell Biol 13:1920–1932

    PubMed  CAS  Google Scholar 

  • Bushman JL, Foiani M, Cigan AM, Paddon CJ, Hinnebusch AG (1993b) Guanine nucleotide exchange factor for eukaryotic translation initiation factor 2 in Saccharomyces cerevisiae: interactions between the essential subunits GCD2, GCD6, and GCD7 and the regulatory subunit GCN3. Mol Cell Biol 13:4618–4631

    PubMed  CAS  Google Scholar 

  • Campbell LE, Wang X, Proud CG (1999) Nutrients differentially regulate multiple translation factors and their control by insulin. Biochem J 344:433–441

    PubMed  CAS  Google Scholar 

  • Carlberg U, Nilsson A, Nygard O (1990) Functional properties of phosphorylated elongation factor 2. Eur J Biochem 191:639–645

    PubMed  CAS  Google Scholar 

  • Chen J, Peterson RT, Schreiber SL (1998) Alpha 4 associates with protein phosphatases 2A, 4 and 6. Biochem Biophys Res Commun 247:827–832

    PubMed  CAS  Google Scholar 

  • Chong KL, Feng L, Schappert K, Meurs E, Donahue TF, Friesen JD, Hovanessian AG, Williams BR (1992) Human p68 kinase exhibits growth suppression in yeast and homology to the translational regulator GCN2. EMBO J 11:1553–1562

    PubMed  CAS  Google Scholar 

  • Chung HY, Nairn AC, Murata K, Brautigan DL (1999) Mutation of Tyr307 and Leu309 in the protein phosphatase 2 A catalytic subunit favors association with the alpha 4 subunit which promotes dephosphorylation of elongation factor-2. Biochemistry 38:10371–10376

    PubMed  CAS  Google Scholar 

  • Cigan AM, Pabich EK, Feng L, Donahue TF (1989) Yeast translation initiation suppressor sui2 encodes the a subunit of eukaryotic initiation factor 2 and shares sequence identity with the human a subunit. Proc Natl Acad Sci USA 86:2784–2788

    PubMed  CAS  Google Scholar 

  • Cigan AM, Foiani M, Hannig E, Hinnebusch AG (1991) Complex formation by positive and negative translational regulators of GCN4. Mol Cell Biol 11:3217–3228

    PubMed  CAS  Google Scholar 

  • Cigan AM, Bushman JL, Boal TR, Hinnebusch AG (1993) A protein complex of translational regulators of GCN4 mRNA is the guanine nucleotide-exchange factor for translation initiation factor 2 in yeast. Proc Natl Acad Sci USA 90:5350–5354

    PubMed  CAS  Google Scholar 

  • Clemens MJ, Galpine A, Austin SA, Panniers R, Henshaw EC, Duncan R, Hershey JWB, Pollard JW (1987) Regulation of polypeptide chain initiation in Chinese Hamster Ovary cells with a temperature- sensitive leucyl-tRNA synthetase. Changes in phosphorylation of initiation factor eIF-2 and in the activity of the guanine nucleotide exchange factor GEF. J Biol Chem 262:767–771

    PubMed  CAS  Google Scholar 

  • Cusack S, Hartlein M, Leberman R (1991) Sequence, structural and evolutionary relationships between class 2 aminoacyl-tRNA synthetases. Nucleic Acids Res 19:3489–3498

    PubMed  CAS  Google Scholar 

  • Davis TA, Nguyen HV, Suryawan A, Bush J, Jefferson LS, Kimball SR (2000) Developmental changes in the stimulation of translation initiation by feeding in muscle and liver of neonatal pigs. Am J Physiol 279:EI226–EI234

    Google Scholar 

  • Dennis PB, Fumagalli S, Thomas G (1999) Target of rapamycin (TOR):balancing the opposing forces of protein synthesis and degradation. Curr Opinion Cell Reg 9:49–54

    CAS  Google Scholar 

  • Dever TE, Feng L, Wek RC, Cigan AM, Donahue TF, Hinnebusch AG (1992) Phosphorylation of initiation factor 2a by protein kinase GCN2 mediates gene-specific translational control of GCN4 in yeast. Cell 68:585–596

    Google Scholar 

  • Dever TE, Chen J-J, Barber GN, Cigan AM, Feng L, Donahue TF, London IM, Katze MG, Hinnebusch AG (1993) Mammalian eukaryotic initiation factor 2a kinases functionally substitute for GCN2 protein kinase in the GCN4 translational control mechanism in yeast. Proc Natl Acad Sci USA 90:4616–4620

    PubMed  CAS  Google Scholar 

  • Dholakia IN, Wahba AJ (1988) Phosphorylation of the guanine nucleotide exchange factor from rabbit reticulocytes regulates its activity in polypeptide chain initiation. Proc Natl Acad Sci USA 85:51–54

    PubMed  CAS  Google Scholar 

  • Di Como CJ, Arndt KT (1996) Nutrients, via the TOR proteins, stimulate the association of Tap42 with type 2A phosphatases. Genes Dev 10:1904–1916

    PubMed  Google Scholar 

  • Didion T, Regenberg B, Jorgensen MU, Kielland-Brandt MC, Andersen HA (1998) The permease homologue Ssyl p controls the expression of amino acid and peptide transporter genes in Saccharomyces cerevisiae. Mol Microbiol 27:643–650

    PubMed  CAS  Google Scholar 

  • Donahue TF, Cigan AM (1988) Genetic selection for mutations that reduce or abolish ribosomal recognition of the HIS4 translational initiation region. Mol Cell Biol 8:2955–2963

    PubMed  CAS  Google Scholar 

  • Donahue TF, Cigan AM, Pabich EK, Valavicius BC (1988) Mutations at a Zn(II) finger motif in the yeast eIF-26 gene alter ribosomal start-site selection during the scanning process. Cell 54:621–632

    PubMed  CAS  Google Scholar 

  • Dufner A, Thomas G (1999) Ribosomal S6 kinase signaling and the control of translation. Exp Cell Res 253:100–109

    PubMed  CAS  Google Scholar 

  • Everson WV, Flaim KE, Susco DM, Kimball SR, Jefferson LS (1989) Effect of amino acid deprivation on initiation of protein synthesis in rat hepatocytes. Am J Physiol 256:C18–C27

    PubMed  CAS  Google Scholar 

  • Fadden P, Haystead TAJ, Lawrence JC (1997) Identification of phosphorylation sites in the translational regulator, PHAS-I, that are controlled by insulin and rapamycin in rat adipocytes. J Biol Chem 272:10240–10247

    PubMed  CAS  Google Scholar 

  • Fox HL, Pham PT, Kimball SR, Jefferson LS, Lynch CJ (1998) Amino acid effects on translational repressor 4E-BPI are mediated primarily by L-Ieucine in isolated adipocytes. Am J Physiol 275:C1232–C1238

    PubMed  CAS  Google Scholar 

  • Garcia-Barrio M, Dong J, Ufano S, Hinnebusch AG (2000) Association of GCNI-GCN20 regulatory complex with the N-terminus of eIF2a kinase GCN2 is required for GCN2 activation. EMBO J 19:1887–1899

    PubMed  CAS  Google Scholar 

  • Gingras A-C, Kennedy SG, O’Leary MA, Sonenberg N, Hay H (1998) 4E-BPl,a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway. Genes Dev 12:502–513

    PubMed  CAS  Google Scholar 

  • Gingras A-C, Gygi SP, Raught B, Polakeiwicz RD, Abraham RT, Hoekstra MF, Aebersold R, Sonenberg N (1999) Regulation of 4E-BPI phosphorylation: a novel two-step mechanism. Genes Dev 13:1422–1437

    PubMed  CAS  Google Scholar 

  • Goldberg Y (1999) Protein phosphatase 2A: who shall regulate the regulator? Biochem Pharm 57:321–328

    PubMed  CAS  Google Scholar 

  • Hara K, Yonezawa K, Kozlowski MT, Sugimoto T, Andrabi K, Weng QP, Kasuga M, Nishimoto I, Avruch J (1997) Regulation of eIF-4E BPI phosphorylation by mTOR. J Biol Chem 272:26457–26463

    PubMed  CAS  Google Scholar 

  • Hara K, Yonezawa K, Weng Q-P, Kozlowski MT, Belham C, Avruch J (1998) Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BPI through a common effector mechanism. J Biol Chem 273:14484–14494

    PubMed  CAS  Google Scholar 

  • Harashima S, Hinnebusch AG (1986) Multiple GCD genes required for repression of GCN4, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae. Mol Cell Biol 6:3990–3998

    PubMed  CAS  Google Scholar 

  • Harashima S, Hannig EM, Hinnebusch AG (1987) Interactions between positive and negative regulators of GCN4 controlling gene expression and entry into the yeast cell cycle. Genetics 117:409–419

    PubMed  CAS  Google Scholar 

  • Haystead TAJ, Haystead CMM, Hu C, Lin T-A, Lawrence JC (1994) Phosphorylation of PHAS-I by mitogen-activated protein (MAP) kinase. Identification of a site phosphorylated by MAP Kinase in vitro and in response to insulin in rat adipocytes. J Biol Chem 269:23185–23191

    PubMed  CAS  Google Scholar 

  • Heesom KJ, Denton RM (1999) Dissociation of the eukaryotic intiation factor-4E/ 4E-BP1 complex involves phosphorylation of 4E-BP1 by an mTOR-associated kinase. Biochem J 457:489–493

    CAS  Google Scholar 

  • Hinnebusch AG (1985) A hierarchy of trans-acting factors modulates translation of an activator of amino acid biosynthetic genes in Saccharomyces cerevisae. Mol Cell Biol 5:2349–2360

    PubMed  CAS  Google Scholar 

  • Hinnebusch AG (I988) Mechanisms of gene regulation in the general control of amino acid biosynthesis in Saccharomyces cerevisiae. Microbiol Rev 52:248–273

    Google Scholar 

  • Hinnebusch AG (I993) Gene-specific translational control of the yeast GCN4 gene by phosphorylation of eukaryotic initiation factor 2. Mol Microbiol 10:215–223

    Google Scholar 

  • Hinnebusch AG (1994) Translational control of GCN4: an in vivo barometer of initiation factor activity. Trends Biochem Sci 19:409–414

    PubMed  CAS  Google Scholar 

  • Hinnebusch AG (I997) Translational regulation of yeast GCN4 - a window on factors that control initiator-tRNA binding to the ribosome. J Biol Chem 272:21661–21664

    Google Scholar 

  • Iiboshi Y, Papst PI, Kawasome H, Hosoi H, Abraham RT, Houghton PJ, Terada N (1999) Amino acid-dependent control of p70S6k. Involvement of tRNA aminoacylation in the regulation. J Biol Chem 274:1092–1099

    PubMed  CAS  Google Scholar 

  • Inui S, Kuwahara K, Mizutani J, Maeda K, Kawai T, Nakayasu H, Sakaguchi N (1995) Molecular cloning of a cDNA clone encoding a phosphoprotein component related to the Ig receptor-mediated signal transduction. J Immunol 154:2714–2723

    PubMed  CAS  Google Scholar 

  • Inui S, Sanjo H, Maeda K, Yamamoto H, Miyamoto E, Sakaguchi N (1998) Ig receptor binding protein 1 (alpha4) is associated with a rapamycin-sensitive signal transduction in lymphocytes through direct binding to the catalytic subunit of protein phosphatase 2A. Blood 92:539–546

    PubMed  CAS  Google Scholar 

  • Iraqui I, Vissers S, Bernard F, De Craene J-O, Boles E, Urrestarazu A, Andre B (1999) Amino acid signaling in Saccharomyces cerevisiae: a permease-like sensor of external amino acids and Fbox protein Grrl p are required for transcriptional induction of the AGPI gene, which encodes a broad-specificity amino acid permease. Mol Cell Biol 19:989–1001

    PubMed  CAS  Google Scholar 

  • Jefferies HBI, Thomas G (1996) Ribosomal protein S6 phosphorylation and signal transduction. In: Hershey JWB, Mathews MB, Sonenberg N (ed) Translational control. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp 389–409

    Google Scholar 

  • Jiang Y, Broach JR (1999) Tor proteins and protein phosphatase 2A reciprocally regulate Tap42 in controlling cell growth in yeast. EMBO J 18:2782–2792

    PubMed  CAS  Google Scholar 

  • JØrgensen MU, Bruun MB, Didion T, Kielland-Brandt MC (I998) Mutations in five loci affecting GAP1-independent uptake of neutral amino acids in yeast. Yeast 14:103–114

    Google Scholar 

  • Kimball SR, Jefferson LS (1991) Mechanism of inhibition of peptide chain initiation by amino acid deprivation in perfused rat liver. Regulation involving inhibition of eukaryotic Initiation Factor 2α phosphatase activity. J Biol Chem 266:1969–1976

    CAS  Google Scholar 

  • Kimball SR, Everson WV, Flaim KE, Jefferson LS (1989) Initiation of protein synthesis in a cellfree system prepared from rat hepatocytes. Am J Physiol 256:C28–C34

    PubMed  CAS  Google Scholar 

  • Kimball SR, Horetsky RL, Jefferson LS (1998) Implication of eIF2B rather than eIF4E in the regulation of global protein synthesis by amino acids in L6 myoblasts. J Biol Chem 273:30945–30953

    PubMed  CAS  Google Scholar 

  • Kimball SR, Shantz LM, Horetsky RL, Jefferson LS (1999) Leucine regulates translation of specific mRNAs in L6 myoblasts through mTOR-mediated changes in availability of eIF4E and phosphorylation of ribosomal protein S6. J Biol Chem 274:11647–11652

    PubMed  CAS  Google Scholar 

  • Kimball SR, Jefferson LS, Davis TA (2000) Feeding stimulates protein synthesis in muscle and liver of neonatal pigs through an mTOR-dependent process. Am J Physiol 279:E1080–E1087

    CAS  Google Scholar 

  • Kishi T, Seno T, Yamao F (1998) Grr1 functions in the ubiquitin pathway in Saccharomyces cerevisiae through association with Skp1. Mol Gen Genet 257:143–148

    PubMed  CAS  Google Scholar 

  • Kleijn M, Scheper GC, Voorma HO, Thomas AAM (1998) Regulation of translation initiation factors by signal transduction. Eur J Biochem 253:531–544

    PubMed  CAS  Google Scholar 

  • Kruckeberg AL, Walsh MC, Van Dam K (1998) How do yeast cells sense glucose? Bioessays 20:972–976

    PubMed  CAS  Google Scholar 

  • Kumar V, Pandey P, Sabatini D, Kumar M, Majumder PK, Bharti A, Carmichael G, Kufe D, Kharbanda S (2000) Functional interaction between RAFT1/FRAP/mTOR and protein kinase Cδ in the regulation of cap-dependent initiation of translation. EMBO J 19:1087–1097

    PubMed  CAS  Google Scholar 

  • Kuwahara K, Matsuo T, Nomura J, Igarashi H, Kimoto M, Inui S, Sakaguchi N (1994) Identification of a 52-kDa molecule (p52) coprecipitated with the Ig receptor-related MB-1 protein that is inducibly phosphorylated by the stimulation with phorbol myristate acetate. J Immunol 152:2742–2752

    PubMed  CAS  Google Scholar 

  • Lafuente MJ, Gancedo C, Jauniaux J-C, Gancedo JM (2000) Mth1 receives the signal given by the glucose sensors Snf3 and Rgt2 in Saccharomyces cerevisiae. Mol Microbiol 35:161–172

    PubMed  CAS  Google Scholar 

  • Li FN, Johnston M (1997) Grr1 of Saccharomyces cerevisiae is connected to the ubiquitin proteolysis machinery through Skp 1: coupling glucose sensing to gene expression and the cell cycle. EMBO J 16:5629–5638

    PubMed  CAS  Google Scholar 

  • Lu JF, O’Hara EB, Trieselmann BA, Romano PR, Dever TE (1999) The interferon-induced doublestranded RNA-activated protein kinase PKR will phosphorylate serine, threonine, or tyrosine at residue 51 in eukaryotic initiation factor 2 alpha. J Biol Chem 274:32198–32203

    PubMed  CAS  Google Scholar 

  • Luke MM, Della Seta F, Di Como CJ, Sugimoto H, Kobayashi R, Arndt KT (1996) The SAP, a new family of proteins, associate and function positively with the SIT4 phosphatase. Mol Cell Biol 16:2744–2755

    PubMed  CAS  Google Scholar 

  • Lynch CG, Fox HL, Vary TC, Jefferson LS, Kimball SR (2000) Regulation of amino acid-sensitive TOR signaling by leucine analogs in adipocytes. J Cell Biochem 77:234–251

    PubMed  CAS  Google Scholar 

  • Marshall-Carlson L, Celenza JL, Laurent BC, Carlson M (1990) Mutational analysis of the SNF3 glucose transporter of Saccharomyces cerevisiae. Mol Cell Biol 10:1105–1115

    PubMed  CAS  Google Scholar 

  • Marton MJ, Crouch D, Hinnebusch AG (1993) GCN1, a translational activator of GCN4 in Saccharomyces cerevisiae, is required for phosphorylation of eukaryotic translation initiation factor 2 by protein kinase GCN2. Mol Cell Biol 13:3541–3556

    PubMed  CAS  Google Scholar 

  • Marton MJ, Vazquez de Aldana CRY, Qiu HF, Chakraburtty K, Hinnebusch AG (1997) Evidence that GCN1 and GCN20, translational regulators of GCN4, function on elongating ribosomes in activation of eIF2-alpha kinase GCN2. Mol Cell Biol 17:4474–4489

    PubMed  CAS  Google Scholar 

  • Merrick WC, Hershey JWB (1996) The pathway and mechanism of eukaryotic protein synthesis. In: Hershey JWB, Mathews MB, Sonenberg N (eds) Translational control. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp 31–69

    Google Scholar 

  • Miller PF, Hinnebusch AG (1989) Sequences that surround the stop codons of upstream open reading frames in GCN4 mRNA determine their distinct functions in translational control. Genes Dev 3:1217–1225

    PubMed  CAS  Google Scholar 

  • Miller PF, Hinnebusch AG (1990) cis-Acting sequences involved in the translational control of GCN4 expression. Biochem Biophys Acta 1050:151–154

    PubMed  CAS  Google Scholar 

  • Miotto G, Venerando R, Khurana KK, Siliprandi N, Mortimore GE (1992) Control of hepatic proteolysis by leucine and isovaleryl-L-carnitine through a common locus. Evidence for a possible mechanism of recognition at the plasma membrane. J Biol Chem 267:22066–22072

    PubMed  CAS  Google Scholar 

  • Mortimore GE, Wert JJ, Miotto G, Venerando R, Kadowaki M (1994) Leucine-specific binding of photoreactive Leu7-MAP to a high molecular weight protein on the plasma membrane of the isolated rat hepatocyte. Biochem Biophys Res Commun 203:200–208

    PubMed  CAS  Google Scholar 

  • Mueller PP, Jackson BM, Miller PF, Hinnebusch AG (1988) The first and fourth upstream open reading frames in GCN4 mRNA have similar initiation efficiencies but respond differently in translational control to change in length and sequence. Mol Cell Biol 8:5439–5447

    PubMed  CAS  Google Scholar 

  • Murata K, Wu J, Brautigan DL (1997) B cell receptor-associated protein a4 displays rapamycinsensitive binding directly to the catalytic subunit of protein phosphatase 2 A. J Biol Chem 94:10624–10629

    CAS  Google Scholar 

  • Nanahoshi M, Nishiuma T, Tsujishita Y, Hara K, Inui S, Sakaguchi N, Yonezawa K (1998) Regulation of protein phosphatase 2 A catalytic activity by alpha4 protein and its yeast homolog Tap42. Biochem Biophys Res Commun 251:520–526

    PubMed  CAS  Google Scholar 

  • Nilsson A, Nygard O (1995) Phosphorylation of eukaryotic elongation factor 2 in differentiating and proliferating HL-60 cells. Biomed Biochim Acta 1268:263–268

    Google Scholar 

  • Oldfield S, Proud CG (1992) Purification, phosphorylation and control of the guanine-nucleotideexchange factor from rabbit reticulocyte Iysates. Eur J Biochem 208:73–81

    PubMed  CAS  Google Scholar 

  • Ozcan S, Dover J, Johnston M (1998) Glucose sensing and signaling by two glucose receptors in the yeast Saccharomyces cerevisiae. EMBO J 17:2566–2573

    PubMed  CAS  Google Scholar 

  • Ozcan S, Johnson M (1999) Function and regulation of yeast hexose transporters. Microbiol Mol Biol Rev 63:554–569

    PubMed  CAS  Google Scholar 

  • Paddon CJ, Hannig EM, Hinnebusch AG (1989) Amino acid sequence similarity between GCN3 and GCD2, positive and negative translational regulators of GCN4: evidence for antagonism by competition. Genetics 122:551–559

    PubMed  CAS  Google Scholar 

  • Pain VM (1996) Initiation of protein synthesis in eukaryotic cells. Eur J Biochem 236:747–771

    PubMed  CAS  Google Scholar 

  • Pain VM, Henshaw EC (1975) Initiation of protein synthesis in Ehrlich ascites tumour cells. Evidence for physiological variation in the association of methionyl-tRNAf with native 40-S ribosomal subunits in vivo. Eur J Biochem 57:335–342

    PubMed  CAS  Google Scholar 

  • Parekh D, Ziegler W, Yonezawa K, Hara K, Parker PJ (1999) Mammalian TOR controls one of two kinase pathways acting upon nPKCo and nPKCf. J Biol Chem 274:34758–34764

    PubMed  CAS  Google Scholar 

  • Patti M-E, Brambilla E, Luzi L, Landaker EJ, Kahn CR (1998) Bidirectional modulation of insulin action by amino acids. J Clin Invest 101:1519–1529

    PubMed  CAS  Google Scholar 

  • Pavitt GD, Ramaiah KVA, Kimball SR, Hinnebusch AG (1997) eIF2 independently binds two distinct eIF2B sub complexes that catalyze and regulate guanine-nucleotide exchange. Genes Dev 12:514–526

    Google Scholar 

  • Pavitt GD, Yang W, Hinnebusch AG (1997) Homologous segments in three subunits of the guanine nucleotide exchange factor eIF2B mediate translational regulation by phosphorylation of eIF2. Mol Cell Biol 17:1298–1313

    PubMed  CAS  Google Scholar 

  • Peterson RT, Desai BN, Hardwick JS, Schreiber SL (1999) Protein phosphatase 2A interacts with the 70-kDa S6 kinase and is activated by inhibition of FKBP12-rapamycin-associated protein. Proc Natl Acad Sci USA 96:4438–4442

    PubMed  CAS  Google Scholar 

  • Peterson RT, Beal PA, Comb MJ, Schreiber SL (2000) FKBP12-rapamycin-associated protein (FRAP) autophosphorylates at serine 2481 under translationally repressive conditions. J Biol Chem 275:7416–7423

    PubMed  CAS  Google Scholar 

  • Pham PT, Heydrick SJ, Fox HL, Kimball SR, Jefferson LS, Lynch CJ (2000) Assessment of cell signaling pathways in the regulation of mTOR by amino acids in rat adipocytes. J Cell Biochem (in press)

    Google Scholar 

  • Pollard JW, Galpine AR, Clemens MJ (1989) A novel role for aminoacyl-tRNA synthetases in the regulation of polypeptide chain initiation. Eur J Biochem 182:1–9

    PubMed  CAS  Google Scholar 

  • Ramirez M, Wek RC, Hinnebusch AG (1991) Ribosome association of GCN2 protein kinase, a translational activator of the GCN4 gene of Saccharomyces cerevisiae. Mol Cell Biol 11:3027–3036

    PubMed  CAS  Google Scholar 

  • Ramirez M, Wek RC, de Aldana CRY, Jackson BM, Freeman B, Hinnebusch AG (1992) Mutations activating the yeast eIF-2a kinase GCN2: isolation of alleles altering the domain related to histidyl-tRNA synthetases. Mol Cell Biol 12:5801–5815

    PubMed  CAS  Google Scholar 

  • Redpath NT, Price NT, Severinov KV, Proud CG (1993) Regulation of elongation factor-2 by multisite phosphorylation. Eur J Biochem 211:689–699

    Google Scholar 

  • Redpath NT, Foulstone EJ, Proud CG (1996) Regulation of translation elongation factor-2 by insulin via a rapamycin-sensitive signalling pathway. EMBO J 15:2291–2297

    PubMed  CAS  Google Scholar 

  • Rhoads RE (1999) Signal transduction pathways that regulate eukaryotic protein synthesis. J Biol Chem 274:30337–30340

    PubMed  CAS  Google Scholar 

  • Romanelli A, Martin KA, Toker A, Blenis J (1999) p70 S6 kinase is regulated by protein kinase Czeta and participates in a phosphoinositide 3-kinase-regulated signalling complex. Mol Cell Biol 19:2921–2928

    PubMed  CAS  Google Scholar 

  • Rosenwald IB, Chen JJ, Wang ST, Savas L, London IM, Pullman J (1999) Upregulation of protein synthesis initiation factor eIF-4E is an early event during colon carcinogenesis. Oncogene 18:2507–2517

    PubMed  CAS  Google Scholar 

  • Roussou I, Thireos G, Hauge BM (1988) Transcriptional-translational regulatory circuit in Saccharomyces cerevisiae which involves the GCN4 transcriptional activator and the GCN2 protein kinase. Mol Cell Biol 8:2132–2139

    PubMed  CAS  Google Scholar 

  • Rowlands AG, Montine KS, Henshaw EC, Panniers R (1988) Physiological stresses inhibit guanine-nucleotide- exchange factor in Ehrlich cells. Eur J Biochem 175:93–99

    PubMed  CAS  Google Scholar 

  • Sachs AB, Sarnow P, Hentze MW (1997) Starting at the beginning, middle, and end - translation initiation in eukaryotes. Cell 89:831–838

    PubMed  CAS  Google Scholar 

  • Santoyo J, Alcalde J, Mendez R, Pulido D, Deharo C (1997) Cloning and characterization of a cDNA encoding a protein synthesis initiation factor-2-alpha (eIF-2-alpha) kinase from Drosophila melanogaster - homology to yeast GCN2 protein kinase. J Biol Chem 272:12544–12550

    PubMed  CAS  Google Scholar 

  • Schmidt A, Beck T, Koller A, Kunz J, Hall MN (1998) The TOR nutrient signaling pathway phosphorylates NPR1 and inhibits turnover of the tryptophan permease. EMBO J 17:6924–6931

    PubMed  CAS  Google Scholar 

  • Schmidt MC, McCartney RR, Zhang X, Tillman TS, Solimeo H, Wölff S, Almonte C, Watkins SC (1999) Std1 and Mth1 proteins interact with the glucose sensors to control glucose-regulated gene expression in Saccharomyces cerevisiae. Mol Cell Biol 19:4561–4571

    PubMed  CAS  Google Scholar 

  • Scorsone KA, Panniers R, Rowlands AG, Henshaw EC (1987) Phosphorylation of eukaryotic initiation factor 2 during physiological stresses which affect protein synthesis. J Biol Chem 262:14538–14543

    PubMed  CAS  Google Scholar 

  • Scott PH, Lawrence JC (1998) Attenuation of mammalian target of rapamycin activity by increased cAMP in 3T3-L1 adipocytes. J Biol Chem 273:34496–34501

    Google Scholar 

  • Scott PH, Brunn GJ, Kohn AD, Roth RA, Lawrence JC (1998) Evidence of insulin-stimulated phosphorylation and activation of the mammalian target of rapamycin mediated by a protein kinase B signaling pathway. Proc Natl Acad Sci USA 95:7772–7777

    PubMed  CAS  Google Scholar 

  • Shigemitsu K, Tsujishita Y, Miyake H, Hidayat S, Tanaka N, Hara K, Yonezawa K (1999) Structural requirement of leucine for activation of p70 S6 kinase. FEBS Lett 447:303–306

    PubMed  CAS  Google Scholar 

  • Singh LP, Aroor AR, Wahba AJ (1994) Phosphorylation of the guanine nucleotide exchange factor and eukaryotic initiation factor 2 by casein kinase II regulates guanine nucleotide binding and GDP/GTP exchange. Biochemistry 33:9152–9157

    PubMed  CAS  Google Scholar 

  • Singh LP, Denslow ND, Wahba AJ (1996) Modulation of rabbit reticulocyte guanine nucleotide exchange factor activity by casein kinases 1 and 2 and glycogen synthase kinase 3. Biochemistry 35:3206–3212

    PubMed  CAS  Google Scholar 

  • Sood R, Porter AC, Olsen D, Cavener DR, Wek RC (2000) A mammalian homologue of GCN2 protein kinase important for translational control by phosphorylation of eukaryotic initiation factor-2α. Genetics 154:787–801

    PubMed  CAS  Google Scholar 

  • Thomas GP, Mathews MB (1984) Alterations of transcription and translation in HeLa cells exposed to amino acid analogs. Mol Cell Biol 4:1063–1072

    PubMed  CAS  Google Scholar 

  • Triana-Alonso FJ, Chakraburtty K, Nierhaus KH (1995) The elongation factor 3 unique in higher fungi and essential for protein biosynthesis is an E site factor. J Biol Chem 270:20473–20478

    PubMed  CAS  Google Scholar 

  • Tzamarias D, Thireos G (1988) Evidence that the GCN2 protein kinase regulates reinitiation by yeast ribosomes. EMBO J 7:3547–3551

    PubMed  CAS  Google Scholar 

  • Vagnoli P, Coons DM, Bisson LF (1998) The C-terminal domain of Snf3p mediates glucose-responsive signal transduction in Saccharomyces cerevisiae. FEMS Microbiol Lett 160:31–36

    PubMed  CAS  Google Scholar 

  • Van Ventrooij WJ, Henshaw EC, Hirsch CA (1970) Nutritional effects on the polyribosome distribution and rate of protein synthesis in Ehrlich ascites tumor cells in culture. J Biol Chem 245:5947–5953

    PubMed  Google Scholar 

  • Van Venrooij WJ, Henshaw EC, Hirsch CA (1972) Effects of deprival of glucose or individual amino acids on polyribosome distribution and rate of protein synthesis in cultured mammalian cells. Biochem Biophys Acta 259:127–137

    PubMed  Google Scholar 

  • Vaughan MH, Hansen BS (1973) Control of initiation of protein synthesis in human cells. Evidence for a role of uncharged transfer ribonucleic acid. J Biol Chem 248:7087–7096

    PubMed  CAS  Google Scholar 

  • Vazquez D (ed) (1979) Inhibitors of protein biosynthesis. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Vazquez de Aldana CR, Marton MJ, Hinnebusch AG (1995) GCN20, a novel ATP binding cassette protein, and GCNI reside in a complex that mediates activation of the eIF-2α kinase GCN2 in amino acid-starved cells. EMBO J 14:3184–3199

    Google Scholar 

  • Venerando R, Miotto G, Kadowaki M, Siliprandi N, Mortimore GE (1994) Multiphasic control of proteolysis by leucine and alanine in the isolated rat hepatocyte. Am J Physiol 266:C455–461

    PubMed  CAS  Google Scholar 

  • Wang X, Campbell LE, Miller CM, Proud CG (1998) Amino acid availability regulates p70 S6 kinase and multiple translation factors. Biochem J 334:261–267

    PubMed  CAS  Google Scholar 

  • Warrington RC, Wratten N, Hechtman R (1977) L-Histidinol inhibits specifically and reversibly protein and ribosomal RNA synthesis in mouse L cells. J Biol Chem 252:5251–5257

    PubMed  CAS  Google Scholar 

  • Wek RC, Jackson BM, Hinnebusch AG (1989) Juxtaposition of domains homologous to protein kinases and histidyl-tRNA synthetases in GCN2 protein suggests a mechanism for coupling GCN4 expression to amino acid availability. Proc Natl Acad Sci USA 86:4579–4583

    Google Scholar 

  • Wek RC, Ramirez M, Jackson BM, Hinnebusch AG (1990) Identification of positive-acting domains in GCN2 protein kinase required for translational activation of GCN4 expression. Mol Cell Biol 10:2820–2831

    PubMed  CAS  Google Scholar 

  • Welsh GI, Proud CG (1993) Glycogen synthase kinase-3 is rapidly inactivated in response to insulin and phosphorylates eukaryotic initiation factor eIF-2B. Biochem J 294:625–629

    PubMed  CAS  Google Scholar 

  • Welsh GI, Miller CM, Loughlin AJ, Price NT, Proud CG (1998) Regulation of eukaryotic initiation factor eIF2B: glycogen synthase kinase-3 phosphorylates a conserved serine which undergoes dephosphorylation in response to insulin. FEBS Lett 421:125–130

    PubMed  CAS  Google Scholar 

  • Williams NP, Mueller PP, Hinnebusch AG (1988) The positive regulatory function of the 5’- proximal open reading frames in GCN4 mRNA can be mimicked by heterologous, short coding sequences. Mol Cell Biol 8:3827–3826

    PubMed  CAS  Google Scholar 

  • Williams NP, Hinnebusch AG, Donahue TF (1989) Mutations in the structural genes for eukaryotic initiation factors 2α and 2β of Saccharomyces cerevisiae disrupt translational control of GCN4 mRNA. Proc Natl Acad Sci USA 86:7515–7519

    PubMed  CAS  Google Scholar 

  • Xu G, Kwon G, Marshall CA, Lin T-A, Lawrence JC, McDaniel ML (1998) Branched-chain amino acids are essential in the regulation of PHAS-I and p70 S6 kinase by pancreatic β-cells. A possible role in protein translation and mitogenic signaling. J Biol Chem 273:28178–28184

    PubMed  CAS  Google Scholar 

  • Yang W, Hinnebusch AG (1996) Identification of a regulatory sub complex in the guanine nucleotide exchange factor eIF2B that mediates inhibition by phosphorylated eIF2. Mol Cell Biol 16:6603–6616

    PubMed  CAS  Google Scholar 

  • Yang D, Brunn GJ, Lawrence JC (1999) Mutational analysis of sites in the translational regulator, PHAS-I, that are selectively phosphorylated by mTOR. FEBS Lett 453:387–390

    PubMed  CAS  Google Scholar 

  • Yoshizawa F, Kimball SR, Jefferson LS (1997) Modulation of translation initiation in rat skeletal muscle and liver in response to food intake. Biochem Biophys Res Commun 240:825–831

    PubMed  CAS  Google Scholar 

  • Yoshizawa F, Kido T, Nagasawa T (1999) Stimulative effect of dietary protein on the phosphorylation of p70 S6 kinase in the skeletal muscle and liver of food-deprived rats. Biosci Biotechnol Biochem 63:1803–1805

    PubMed  CAS  Google Scholar 

  • Zhu SH, Wek RC (1998) Ribosome-binding domain of eukaryotic initiation factor-2 kinase GCN2 facilitates translation control. J Biol Chem 273:1808–1814

    PubMed  CAS  Google Scholar 

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  1. Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, 17033, USA

    Scot R. Kimball

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  1. Department of Biochemistry and Molecular Biology, Louisiana State University Health Sciences Center, Shreveport, LA, 71130, USA

    Robert E. Rhoads

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Kimball, S.R. (2001). Regulation of Translation Initiation by Amino Acids in Eukaryotic Cells. In: Rhoads, R.E. (eds) Signaling Pathways for Translation. Progress in Molecular and Subcellular Biology, vol 26. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-56688-2_6

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  • DOI: https://doi.org/10.1007/978-3-642-56688-2_6

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