Christopher G Proud

Summary

Affiliation: University of Dundee
Country: UK

Publications

  1. ncbi request reprint eIF2 and the control of cell physiology
    Christopher G Proud
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dunde DD15EH, United Kingdom
    Semin Cell Dev Biol 16:3-12. 2005
  2. ncbi request reprint Interplay between insulin and nutrients in the regulation of translation factors
    C G Proud
    Division of Molecular Physiology, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    Biochem Soc Trans 29:541-7. 2001
  3. ncbi request reprint Regulation of mammalian translation factors by nutrients
    Christopher G Proud
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, MSI WTB complex, Dow Street, UK
    Eur J Biochem 269:5338-49. 2002
  4. ncbi request reprint Role of mTOR signalling in the control of translation initiation and elongation by nutrients
    C G Proud
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, MSI WTB complex, Dundee, DD1 5EH, UK
    Curr Top Microbiol Immunol 279:215-44. 2004
  5. ncbi request reprint mTOR-mediated regulation of translation factors by amino acids
    Christopher G Proud
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Biochem Biophys Res Commun 313:429-36. 2004
  6. ncbi request reprint Regulation of mRNA translation
    C G Proud
    Division of Molecular Physiology, School of Life Sciences, MSI WTB complex, University of Dundee, Dundee DD1 5EH, U K
    Essays Biochem 37:97-108. 2001
  7. ncbi request reprint Ras, PI3-kinase and mTOR signaling in cardiac hypertrophy
    Christopher G Proud
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Cardiovasc Res 63:403-13. 2004
  8. pmc Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteins
    Xuemin Wang
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dow St, Dundee DD1 5EH, United Kingdom
    Mol Cell Biol 25:2558-72. 2005
  9. pmc The C terminus of initiation factor 4E-binding protein 1 contains multiple regulatory features that influence its function and phosphorylation
    Xuemin Wang
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    Mol Cell Biol 23:1546-57. 2003
  10. ncbi request reprint The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses
    Ewan M Smith
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    J Biol Chem 280:18717-27. 2005

Collaborators

Detail Information

Publications86

  1. ncbi request reprint eIF2 and the control of cell physiology
    Christopher G Proud
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dunde DD15EH, United Kingdom
    Semin Cell Dev Biol 16:3-12. 2005
    ....
  2. ncbi request reprint Interplay between insulin and nutrients in the regulation of translation factors
    C G Proud
    Division of Molecular Physiology, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    Biochem Soc Trans 29:541-7. 2001
    ..eEF2 kinase is phosphorylated by p70 S6 kinase at Ser-366; this results in the inactivation of eEF2 kinase, especially at low (micromolar) Ca concentrations...
  3. ncbi request reprint Regulation of mammalian translation factors by nutrients
    Christopher G Proud
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, MSI WTB complex, Dow Street, UK
    Eur J Biochem 269:5338-49. 2002
    ..Since control of eIF2B is independent of mTOR, these data indicate the operation of additional, and so far unknown, regulatory mechanisms that control eIF2B activity...
  4. ncbi request reprint Role of mTOR signalling in the control of translation initiation and elongation by nutrients
    C G Proud
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, MSI WTB complex, Dundee, DD1 5EH, UK
    Curr Top Microbiol Immunol 279:215-44. 2004
    ....
  5. ncbi request reprint mTOR-mediated regulation of translation factors by amino acids
    Christopher G Proud
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Biochem Biophys Res Commun 313:429-36. 2004
    ..Ser78 is not phosphorylated by known components of the mTOR pathway implying the existence of novel mTOR-regulated kinases that control eEF2 kinase...
  6. ncbi request reprint Regulation of mRNA translation
    C G Proud
    Division of Molecular Physiology, School of Life Sciences, MSI WTB complex, University of Dundee, Dundee DD1 5EH, U K
    Essays Biochem 37:97-108. 2001
    ..During development, control of mRNA translation regulates gene expression both spatially and temporally...
  7. ncbi request reprint Ras, PI3-kinase and mTOR signaling in cardiac hypertrophy
    Christopher G Proud
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Cardiovasc Res 63:403-13. 2004
    ....
  8. pmc Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteins
    Xuemin Wang
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dow St, Dundee DD1 5EH, United Kingdom
    Mol Cell Biol 25:2558-72. 2005
    ..These data have important implications for understanding signaling downstream of mTOR and the development of new strategies to impair mTOR signaling...
  9. pmc The C terminus of initiation factor 4E-binding protein 1 contains multiple regulatory features that influence its function and phosphorylation
    Xuemin Wang
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    Mol Cell Biol 23:1546-57. 2003
    ..However, in 4E-BP3, replacement of the alanine at the position corresponding to S112 by serine or glutamate did not confer the ability to be released from eIF4E in response to insulin...
  10. ncbi request reprint The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses
    Ewan M Smith
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    J Biol Chem 280:18717-27. 2005
    ..This likely involves the phosphorylation of the elongation factor-2 kinase by the AMP-activated protein kinase...
  11. pmc The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization
    Gert C Scheper
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee, United Kingdom
    Mol Cell Biol 23:5692-705. 2003
    ..Within the nucleus, Mnk2b and certain variants of Mnk2a that are present in the nucleus colocalize with the promyelocytic leukemia protein PML, which also binds to eIF4E...
  12. pmc Regulation of targets of mTOR (mammalian target of rapamycin) signalling by intracellular amino acid availability
    Anne Beugnet
    School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Scotland, UK
    Biochem J 372:555-66. 2003
    ..These and other data presented in the current study are consistent with the idea that it is intracellular amino acid levels that regulate mTOR signalling...
  13. pmc A novel mTOR-regulated phosphorylation site in elongation factor 2 kinase modulates the activity of the kinase and its binding to calmodulin
    Gareth J Browne
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    Mol Cell Biol 24:2986-97. 2004
    ..eEF2 kinase is thus a target for mTOR signaling independently of previously known downstream components of the pathway...
  14. ncbi request reprint Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398
    Gareth J Browne
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom
    J Biol Chem 279:12220-31. 2004
    ..Thus, AMPK and eEF2 kinase may provide a key link between cellular energy status and the inhibition of protein synthesis, a major consumer of metabolic energy...
  15. ncbi request reprint Target of rapamycin (TOR)-signaling and RAIP motifs play distinct roles in the mammalian TOR-dependent phosphorylation of initiation factor 4E-binding protein 1
    Anne Beugnet
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    J Biol Chem 278:40717-22. 2003
    ..The RAIP motif thus promotes the mTOR-dependent phosphorylation of multiple sites in 4E-BP1 independently of the 4E-BP1/raptor interaction...
  16. pmc cdc2-cyclin B regulates eEF2 kinase activity in a cell cycle- and amino acid-dependent manner
    Ewan M Smith
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee, UK
    EMBO J 27:1005-16. 2008
    ..These data closely match the control of Ser359 phosphorylation and indicate that cdc2 may be regulated by mTORC1...
  17. ncbi request reprint Features in the N and C termini of the MAPK-interacting kinase Mnk1 mediate its nucleocytoplasmic shuttling
    Josep Lluís Parra-Palau
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dow St, Dundee DD1 5EH, United Kingdom
    J Biol Chem 278:44197-204. 2003
    ..Mutations that reduce the binding of Mnk1 to eIF4G in vivo and in vitro also decrease the ability of Mnk1 to enhance eIF4E phosphorylation in vivo, underlining the importance of the eIF4G-Mnk1 interaction in this process...
  18. pmc Activation of protein synthesis in cardiomyocytes by the hypertrophic agent phenylephrine requires the activation of ERK and involves phosphorylation of tuberous sclerosis complex 2 (TSC2)
    Mark Rolfe
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, MSI WTB complex, Dow Street, Dundee DD1 5EH, UK
    Biochem J 388:973-84. 2005
    ....
  19. ncbi request reprint Regulation of the phosphorylation of elongation factor 2 by MEK-dependent signalling in adult rat cardiomyocytes
    Lijun Wang
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee, UK
    FEBS Lett 531:285-9. 2002
    ..Expression of an activated form of MEK leads to dephosphorylation of eEF2, in an mTOR independent manner, indicating that signalling via MEK/Erk suffices to cause dephosphorylation of eEF2...
  20. pmc Ca(2+)-independent protein kinase C activity is required for alpha1-adrenergic-receptor-mediated regulation of ribosomal protein S6 kinases in adult cardiomyocytes
    Lijun Wang
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Biochem J 373:603-11. 2003
    ..Our data thus suggest that Ca(2+)-independent PKC isoforms play an important role in coupling the alpha(1)-adrenergic receptor to mTOR signalling and protein synthesis in adult cardiomyocytes...
  21. pmc The Drosophila protein kinase LK6 is regulated by ERK and phosphorylates the eukaryotic initiation factor eIF4E in vivo
    Josep L Parra-Palau
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, MSI WTB complex, Dow Street, Dundee DD1 5EH, UK
    Biochem J 385:695-702. 2005
    ..These results show that LK6 binds to ERK and is activated by ERK signalling and it is responsible for phosphorylating eIF4E in Drosophila...
  22. ncbi request reprint Localisation and regulation of the eIF4E-binding protein 4E-BP3
    Miranda Kleijn
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, DD1 5EH, Dundee, UK
    FEBS Lett 532:319-23. 2002
    ..Furthermore, 4E-BP3/eIF4E association in the cytoplasm was regulated by serum or interleukin-2 starvation in the different cell types. Rapamycin did not affect the association of eIF4E with 4E-BP3 in the cytoplasm or in the nucleus...
  23. ncbi request reprint Ras/Erk signaling is essential for activation of protein synthesis by Gq protein-coupled receptor agonists in adult cardiomyocytes
    Lijun Wang
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee, UK
    Circ Res 91:821-9. 2002
    ..This study provides new insights into the mechanisms underlying the stimulation of protein synthesis by hypertrophic agents in heart...
  24. ncbi request reprint Analysis of mTOR signaling by the small G-proteins, Rheb and RhebL1
    Andrew R Tee
    University of Dundee, Medical Sciences Institute Wellcome Building Complex, Dow Street, Dundee DD1 5EH, UK
    FEBS Lett 579:4763-8. 2005
    ..Mutation of Rheb and RhebL1 at N41 impaired their interaction with mTOR, which identifies mTOR as a common downstream target of both Rheb and RhebL1...
  25. pmc ABC50 promotes translation initiation in mammalian cells
    Sonia Paytubi
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom
    J Biol Chem 284:24061-73. 2009
    ..Taken together, the present data show that ABC50 plays a key role in translation initiation and has functions that are distinct from those of other non-membrane ABC proteins...
  26. pmc Muscarinic receptor-mediated activation of p70 S6 kinase 1 (S6K1) in 1321N1 astrocytoma cells: permissive role of phosphoinositide 3-kinase
    Xiuwen Tang
    Division of Cell Signalling, School of Life Sciences, MSI WTB complex, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 374:137-43. 2003
    ..Moreover, 4E-BP1 and hence, presumably, mTOR can be regulated independently of PI3K activation through these mechanisms...
  27. pmc Caspase cleavage of initiation factor 4E-binding protein 1 yields a dominant inhibitor of cap-dependent translation and reveals a novel regulatory motif
    Andrew R Tee
    Division of Molecular Physiology, School of Life Sciences, Medical Sciences Institute, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    Mol Cell Biol 22:1674-83. 2002
    ..This suggests that the N-terminal sequence of 4E-BP1 is required for optimal regulation of 4E-BPs by insulin...
  28. ncbi request reprint The N-terminal region of ABC50 interacts with eukaryotic initiation factor eIF2 and is a target for regulatory phosphorylation by CK2
    Sonia Paytubi
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, UK
    Biochem J 409:223-31. 2008
    ..Expression of a mutant of ABC50 in which both sites are mutated to alanine markedly decreased the association of eIF2 with 80S ribosomal and polysomal fractions...
  29. ncbi request reprint Cross-talk between the ERK and p70 S6 kinase (S6K) signaling pathways. MEK-dependent activation of S6K2 in cardiomyocytes
    L Wang
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, United Kingdom
    J Biol Chem 276:32670-7. 2001
    ..Another hypertrophic agent, endothelin 1, also activated S6K2 in a MEK-dependent manner. Our findings provide strong evidence for novel signaling connections between MEK/ERK and S6K2...
  30. pmc The regulation of protein synthesis and translation factors by CD3 and CD28 in human primary T lymphocytes
    Miranda Kleijn
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee, MSI Wellcome Trust Biocentre, DD1 5EH United Kingdom
    BMC Biochem 3:11. 2002
    ..We studied the regulation of protein synthesis after 1 h of activation using alphaCD3 antibody to stimulate the T cell receptor and alphaCD28 antibody to provide the co-stimulus...
  31. pmc Mutations linked to leukoencephalopathy with vanishing white matter impair the function of the eukaryotic initiation factor 2B complex in diverse ways
    Wei Li
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    Mol Cell Biol 24:3295-306. 2004
    ..We provide evidence that expression of VWM mutant eIF2B may enhance the translation of specific mRNAs. The variability of the clinical phenotype in VWM may reflect the multiple ways in which VWM mutations affect eIF2B function...
  32. ncbi request reprint The PSF.p54nrb complex is a novel Mnk substrate that binds the mRNA for tumor necrosis factor alpha
    Maria Buxade
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee, UK
    J Biol Chem 283:57-65. 2008
    ..These findings identify a novel Mnk substrate. They also suggest that the Mnk-catalyzed phosphorylation of PSF may regulate the fate of specific mRNAs by modulating their binding to PSF.p54(nrb)...
  33. pmc Glucose exerts a permissive effect on the regulation of the initiation factor 4E binding protein 4E-BP1
    J Patel
    Division of Molecular Physiology, School of Life Sciences, MSI/WTB Complex, Dow Street, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 358:497-503. 2001
    ..Taken together with earlier data showing that amino acids regulate 4E-BP1 and p70 S6k, the present findings show that 4E-BP1 in particular is regulated in response to the availability of both amino acids and sugars...
  34. pmc The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a eukaryotic initiation factor 4E kinase with high levels of basal activity in mammalian cells
    G C Scheper
    School of Life Sciences, University of Dundee, Dundee, United Kingdom
    Mol Cell Biol 21:743-54. 2001
    ..This might reflect a mechanism to ensure rapid, but transient, phosphorylation of eIF4E upon stimulation of the MAPK pathways...
  35. ncbi request reprint Features of the catalytic domains and C termini of the MAPK signal-integrating kinases Mnk1 and Mnk2 determine their differing activities and regulatory properties
    Josep Lluis Parra
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, UK
    J Biol Chem 280:37623-33. 2005
    ..These data indicate that multiple features determine the activities of the Mnks and thus impact on their ability to phosphorylate physiological substrates such as eukaryotic initiation factor 4E...
  36. ncbi request reprint The extracellular signal-regulated kinase pathway regulates the phosphorylation of 4E-BP1 at multiple sites
    Terence P Herbert
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, United Kingdom
    J Biol Chem 277:11591-6. 2002
    ..In conclusion, the Erk pathway, via mechanisms also requiring mTOR, regulates the phosphorylation of multiple sites in 4E-BP1 in vivo and this is sufficient for the release of 4E-BP1 from eIF4E...
  37. pmc Evidence that the dephosphorylation of Ser(535) in the epsilon-subunit of eukaryotic initiation factor (eIF) 2B is insufficient for the activation of eIF2B by insulin
    Xuemin Wang
    Division of Molecular Physiology, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U K
    Biochem J 367:475-81. 2002
    ....
  38. pmc Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase
    X Wang
    Division of Molecular Physiology and MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dundee DD1 5EH, UK
    EMBO J 20:4370-9. 2001
    ..In contrast, regulation of eEF2 by stimuli that activate Erk is insensitive to rapamycin, but blocked by inhibitors of MEK/Erk signalling, consistent with the involvement of p90(RSK1)...
  39. ncbi request reprint The multifaceted role of mTOR in cellular stress responses
    Christopher G Proud
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, Dow Street, Dundee, DD1 5EH, UK
    DNA Repair (Amst) 3:927-34. 2004
    ..However, these responses make physiological sense, as impairment of mTOR signalling under these conditions will tend to inhibit anabolic processes and cell growth and division...
  40. ncbi request reprint Regulation of peptide-chain elongation in mammalian cells
    Gareth J Browne
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, MSI WTB complex, Dundee, UK
    Eur J Biochem 269:5360-8. 2002
    ..Conversely, eEF2 is inactivated by phosphorylation in response to stimuli that increase energy demand or reduce its supply. This likely serves to slow down protein synthesis and thus conserve energy under such circumstances...
  41. pmc Pharmacological and genetic evaluation of proposed roles of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), extracellular signal-regulated kinase (ERK), and p90(RSK) in the control of mTORC1 protein signaling by phorbo
    Bruno D Fonseca
    Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    J Biol Chem 286:27111-22. 2011
    ..This study provides important information for the design of efficient strategies to combat the hyperactivation of mTORC1 signaling by oncogenic pathways...
  42. ncbi request reprint Control of the translational machinery in mammalian cells
    Christopher G Proud
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, MSI WTB, CoMPLEX, Dow Street, UK
    Eur J Biochem 269:5337. 2002
  43. ncbi request reprint Does phosphorylation of the cap-binding protein eIF4E play a role in translation initiation?
    Gert C Scheper
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, MSI WTB complex, Dow Street, UK
    Eur J Biochem 269:5350-9. 2002
    ..The implications of these studies are discussed in the light of other, in vitro and in vivo, investigations designed to address the role of eIF4E phosphorylation in mRNA translation or its control...
  44. ncbi request reprint Phosphorylated seryl and threonyl, but not tyrosyl, residues are efficient specificity determinants for GSK-3beta and Shaggy
    D D Williams
    Department of Anatomy and Physiology, University of Dundee, UK
    FEBS Lett 448:86-90. 1999
    ..This unpredicted efficacy of Thr(P) in the priming position suggests that there may be other unidentified substrates for these kinases...
  45. ncbi request reprint Intracellular sensing of amino acids in Xenopus laevis oocytes stimulates p70 S6 kinase in a target of rapamycin-dependent manner
    Graham R Christie
    Medical Research Council Nutrient Sensing and Signaling Group, Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee, DD1 5EH, Scotland
    J Biol Chem 277:9952-7. 2002
    ....
  46. ncbi request reprint Phosphorylation of eukaryotic initiation factor 4E markedly reduces its affinity for capped mRNA
    Gert C Scheper
    School of Life Sciences, MSI WTB complex, University of Dundee, Dundee DD1 5EH, United Kingdom
    J Biol Chem 277:3303-9. 2002
    ..The implications of our findings for the mechanism of translation initiation are discussed...
  47. pmc Eukaryotic initiation factor 2B: identification of multiple phosphorylation sites in the epsilon-subunit and their functions in vivo
    X Wang
    Division of Molecular Physiology, School of Life Sciences and MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dundee DD1 5EH, UK
    EMBO J 20:4349-59. 2001
    ..The fifth site, which lies outside the catalytic domain of eIF2Bepsilon, can be phosphorylated by casein kinase 1. All five sites are phosphorylated in the eIF2B complex in vivo...
  48. ncbi request reprint ATP depletion increases phosphorylation of elongation factor eEF2 in adult cardiomyocytes independently of inhibition of mTOR signalling
    Laura E McLeod
    Division of Molecular Physiology, Faculty of Life Sciences, University of Dundee, DD1 5EH, Dundee, UK
    FEBS Lett 531:448-52. 2002
    ..Only at later times is an effect on mTOR signalling observed. These data suggest that energy depletion leads to inhibition of protein synthesis through phosphorylation of eEF2 independently of inhibition of mTOR signalling...
  49. pmc Glucose and amino acids modulate translation factor activation by growth factors in PC12 cells
    M Kleijn
    Department of Anatomy and Physiology, MSI Wellcome Trust Building, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 347:399-406. 2000
    ..Thus the ERK pathway plays a key role in the regulation of protein synthesis in PC12 cells...
  50. ncbi request reprint Rapid induction of apoptosis mediated by peptides that bind initiation factor eIF4E
    T P Herbert
    Department of Anatomy and Physiology, MSI WTB complex, University of Dundee, UK
    Curr Biol 10:793-6. 2000
    ..Thus these new data indicate that eIF4E has a direct role in controlling cell survival that is not linked to its known role in mRNA translation...
  51. ncbi request reprint The activation of eukaryotic initiation factor (eIF)2B by growth factors in PC12 cells requires MEK/ERK signalling
    M Kleijn
    Department of Anatomy and Physiology, University of Dundee, MSI Wellcome Trust Building, Dow Street, DD1 5EH, Dundee, UK
    FEBS Lett 476:262-5. 2000
    ..Thus, the EGF- and NGF-induced activation of eIF2B in PC12 cells involves regulatory mechanisms distinct from dephosphorylation of the GSK-3 site...
  52. pmc The kinase DYRK phosphorylates protein-synthesis initiation factor eIF2Bepsilon at Ser539 and the microtubule-associated protein tau at Thr212: potential role for DYRK as a glycogen synthase kinase 3-priming kinase
    Y L Woods
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, Dow Street, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 355:609-15. 2001
    ..Phosphorylation of Thr(212) primes tau for phosphorylation by GSK3 at Ser(208) in vitro, suggesting a more general role for DYRK isoforms in priming phosphorylation of GSK3 substrates...
  53. ncbi request reprint Eukaryotic initiation factors 4A (eIF4A) and 4G (eIF4G) mutually interact in a 1:1 ratio in vivo
    W Li
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, United Kingdom
    J Biol Chem 276:29111-5. 2001
    ..The data imply that the second binding site in mammalian eIF4A does not bind an additional eIF4A molecule and that initiation factor complexes in different eukaryotes contain one eIF4A per eIF4G...
  54. ncbi request reprint Distinct signalling pathways mediate insulin and phorbol ester-stimulated eukaryotic initiation factor 4F assembly and protein synthesis in HEK 293 cells
    T P Herbert
    Department of Anatomy, The Medical Sciences Institute, University of Dundee, Dow Street, Dundee DD1 5EH, United Kingdom
    J Biol Chem 275:11249-56. 2000
    ..This report also provides evidence that increased eIF4E phosphorylation alone does not affect the assembly of the eIF4F complex or general protein synthesis...
  55. ncbi request reprint Staurosporine inhibits phosphorylation of translational regulators linked to mTOR
    A R Tee
    School of Life Sciences, Medical Sciences Institute Wellcome Trust Building Complex, University of Dundee, Dow Street, Dundee, DD1 5EH, UK
    Cell Death Differ 8:841-9. 2001
    ..It is becoming clear that agents which cause apoptosis inactivate mTOR signalling as a common early response prior to the execution of apoptosis, i.e., before caspase activation...
  56. doi request reprint Protein synthesis and its control in neuronal cells with a focus on vanishing white matter disease
    Graham D Pavitt
    Faculty of Life Sciences, The University of Manchester, Manchester M13 9PT, UK
    Biochem Soc Trans 37:1298-310. 2009
    ..VWM/CACH is caused by mutations in the translation initiation factor, eIF2B, a component of the basal translational machinery in all cells...
  57. ncbi request reprint Differing substrate specificities of members of the DYRK family of arginine-directed protein kinases
    Linda E Campbell
    Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    FEBS Lett 510:31-6. 2002
    ..This study reveals both similarities and differences in the specificities of these arginine-dependent protein kinases...
  58. ncbi request reprint Characterization of the initiation factor eIF2B and its regulation in Drosophila melanogaster
    D D Williams
    School of Life Sciences, Medical Sciences Institute Wellcome Trust Biocentre Complex, University of Dundee, Dundee DD1 5EH, United Kingdom
    J Biol Chem 276:3733-42. 2001
    ..eIF2alpha phosphorylation is also increased by endoplasmic reticulum stress in S2 cells. These are the first data concerning the structure, function or control of eIF2B from D. melanogaster...
  59. ncbi request reprint ABC50 interacts with eukaryotic initiation factor 2 and associates with the ribosome in an ATP-dependent manner
    J K Tyzack
    MSI WTB complex, University of Dundee, Dundee, DD1 5EH, United Kingdom
    J Biol Chem 275:34131-9. 2000
    ..Thus, these data identify ABC50 as a third ABC protein with a likely function in mRNA translation, which associates with eIF2 and with ribosomes...
  60. ncbi request reprint Eukaryotic translation initiation factor 5 (eIF5) acts as a classical GTPase-activator protein
    F E Paulin
    School of Life Sciences, University of Dundee, DD1 5EH, Dundee, Scotland, United Kingdom
    Curr Biol 11:55-9. 2001
    ..Indeed, inspection of their sequences suggests that other translation factors may also act as GAPs...
  61. ncbi request reprint Cleavage of translation initiation factor 4AI (eIF4AI) but not eIF4AII by foot-and-mouth disease virus 3C protease: identification of the eIF4AI cleavage site
    W Li
    School of Life Sciences, MSI/WTB Complex, University of Dundee, Dundee, UK
    FEBS Lett 507:1-5. 2001
    ..The N- and C-terminal cleavage products of eIF4AI generated by FMDV 3C dissociate. Cleavage of eIF4AI by FMDV 3C is thus expected to inactivate it...
  62. ncbi request reprint Characterization of the mammalian initiation factor eIF2B complex as a GDP dissociation stimulator protein
    D D Williams
    School of Life Sciences, Medical Sciences Institute Wellcome Trust Biocentre Complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    J Biol Chem 276:24697-703. 2001
    ..Supplementation of such preparations with recombinant eIF2Balpha markedly enhances activity, indicating that eIF2Balpha is required for full activity of mammalian eIF2B...
  63. pmc A novel mechanism for the control of translation initiation by amino acids, mediated by phosphorylation of eukaryotic initiation factor 2B
    Xuemin Wang
    Department of Biochemistry and Molecular Biology, University of British Columbia, Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada
    Mol Cell Biol 28:1429-42. 2008
    ..These findings identify a new way in which amino acids regulate a key step in translation initiation and indicate that this involves a novel amino acid-sensitive signaling mechanism...
  64. ncbi request reprint Cell signaling. mTOR, unleashed
    Christopher G Proud
    Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T 1Z3, Canada
    Science 318:926-7. 2007
  65. ncbi request reprint ANG II activates effectors of mTOR via PI3-K signaling in human coronary smooth muscle cells
    Sassan Hafizi
    Department of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, Heart Science Centre, Harefield Hospital, Middlesex, United Kingdom
    Am J Physiol Heart Circ Physiol 287:H1232-8. 2004
    ..These signaling mechanisms may mediate the growth-promoting effect of ANG II in human cSMCs...
  66. ncbi request reprint Methods for studying signal-dependent regulation of translation factor activity
    Xuemin Wang
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, Canada
    Methods Enzymol 431:113-42. 2007
    ..In addition, we provide guidelines on using small molecule inhibitors to assess the involvement of specific signaling pathways in controlling translation factors and protein synthesis...
  67. doi request reprint The binding of PRAS40 to 14-3-3 proteins is not required for activation of mTORC1 signalling by phorbol esters/ERK
    Bruno D Fonseca
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC V6T1Z3, Canada
    Biochem J 411:141-9. 2008
    ..Indeed, our results suggest that PRAS40 may not actually be involved in controlling mTORC1, but rather be a downstream target of mTORC1 that is regulated in response only to specific stimuli, such as insulin...
  68. ncbi request reprint Mechanisms underlying suppression of protein synthesis induced by transient focal cerebral ischemia in mouse brain
    Thorsten Mengesdorf
    Department of Experimental Neurology, Max Planck Institute for Neurological Research, 50931, Koln, Germany
    Exp Neurol 177:538-46. 2002
    ....
  69. doi request reprint Analysis of the regulatory motifs in eukaryotic initiation factor 4E-binding protein 1
    Vivian H Y Lee
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada
    FEBS J 275:2185-99. 2008
    ..These data provide important information on the structural requirements for efficient signalling downstream of mTORC1...
  70. ncbi request reprint The Mnks: MAP kinase-interacting kinases (MAP kinase signal-integrating kinases)
    Maria Buxade
    Immunopathology Unit, Department of Experimental and Health Sciences, Pompeu Fabra University, Doctor Aiguader 88, 08003 Barcelona, Spain
    Front Biosci 13:5359-73. 2008
    ..Mnks may also control production of inflammatory mediators and signaling from tyrosine kinase receptors, as well as cell proliferation or survival...
  71. doi request reprint Protein kinase D is a key regulator of cardiomyocyte lipoprotein lipase secretion after diabetes
    Min Suk Kim
    Faculty of Pharmaceutical Sciences, Vancouver, BC, Canada
    Circ Res 103:252-60. 2008
    ..Results from this study could help in restricting cardiac LPL translocation, leading to strategies that overcome contractile dysfunction after diabetes...
  72. pmc Protein kinase C phosphorylates ribosomal protein S6 kinase betaII and regulates its subcellular localization
    Taras Valovka
    Ludwig Institute for Cancer Research, London W1W 7BS, United Kingdom
    Mol Cell Biol 23:852-63. 2003
    ..Taken together, this study uncovers a novel mechanism for the regulation of nucleocytoplasmic shuttling of S6KbetaII by PKC-mediated phosphorylation...
  73. ncbi request reprint Cellular stresses profoundly inhibit protein synthesis and modulate the states of phosphorylation of multiple translation factors
    Jashmin Patel
    Department of Biosciences, University of Kent at Canterbury, Canterbury, UK
    Eur J Biochem 269:3076-85. 2002
    ..Our data reveal that these stress-inducing agents, which are widely used to study stress-signalling in mammalian cells, exert multiple and complex inhibitory effects on the translational machinery...
  74. ncbi request reprint Translation matters: protein synthesis defects in inherited disease
    Gert C Scheper
    Department of Child Neurology Center for Neurogenomics and Cognitive Research, Vrije Universiteit Medical Center, De Boelelaan 1117, 1081HV Amsterdam, The Netherlands
    Nat Rev Genet 8:711-23. 2007
    ..Given the numerous proteins involved in mRNA translation, it is likely that further inherited diseases will turn out to be caused by mutations in genes that are involved in this complex process...
  75. ncbi request reprint Activation of AMP-activated protein kinase inhibits protein synthesis associated with hypertrophy in the cardiac myocyte
    Anita Y M Chan
    Cardiovascular Research Group, Department of Pediatrics, Faculty of Medicine, University of Alberta, Edmonton, Alberta T6G 2S2, Canada
    J Biol Chem 279:32771-9. 2004
    ..Together, our data suggest that the inhibition of protein synthesis by pharmacological activation of AMPK may be a key regulatory mechanism by which hypertrophic growth can be controlled...
  76. ncbi request reprint Engineering mRNA translation initiation to enhance transient gene expression in chinese hamster ovary cells
    Michele F Underhill
    Research School of Biosciences, University of Kent at Canterbury, UK
    Biotechnol Prog 19:121-9. 2003
    ..This work therefore forms the basis of a rational strategy to generically up-regulate transient expression of recombinant proteins by simultaneous host cell engineering...
  77. ncbi request reprint The Mnks are novel components in the control of TNF alpha biosynthesis and phosphorylate and regulate hnRNP A1
    Maria Buxade
    Departament de Fisiologia, Universitat de Barcelona, Spain
    Immunity 23:177-89. 2005
    ..Moreover, Mnk-mediated phosphorylation decreases binding of hnRNP A1 to TNFalpha-ARE in vitro or TNFalpha-mRNA in vivo. Therefore, Mnks are novel players in cytokine regulation and potential new targets for anti-inflammatory therapy...
  78. ncbi request reprint Regulation of protein synthesis in lymphoblasts from vanishing white matter patients
    Barbara Van Kollenburg
    Dept of Pediatrics Child Neurology, VU University Medical Center, Amsterdam, The Netherlands
    Neurobiol Dis 21:496-504. 2006
    ..These findings could form part of the explanation for the episodes of rapid and severe deterioration in VWM patients that are precipitated by febrile infections...
  79. ncbi request reprint Translational regulation of terminal oligopyrimidine mRNAs induced by serum and amino acids involves distinct signaling events
    Sara Caldarola
    Department of Biology, University Tor Vergata, Rome 00133, Italy
    J Biol Chem 279:13522-31. 2004
    ..Interestingly, rapamycin treatment suggests a novel connection between the mTOR pathway and eukaryotic initiation factor-2alpha phosphorylation in mammalian cells, which may not, however, be involved in TOP mRNA translational regulation...
  80. ncbi request reprint Structure of the eukaryotic initiation factor (eIF) 5 reveals a fold common to several translation factors
    Maria R Conte
    Biophysics Laboratories, School of Biological Sciences, University of Portsmouth, Portsmouth PO1 2DT, United Kingdom
    Biochemistry 45:4550-8. 2006
    ..These results reveal a novel protein fold common to several factors involved in related steps of translation initiation. The implications of these observations are discussed in terms of the mechanism of translation initiation...
  81. ncbi request reprint Quantitative proteomics identifies Gemin5, a scaffolding protein involved in ribonucleoprotein assembly, as a novel partner for eukaryotic initiation factor 4E
    Ivo Fierro-Monti
    Department of Biochemistry and Molecular Biology, University of Southern Denmark
    J Proteome Res 5:1367-78. 2006
    ..Our results demonstrate that our quantitative proteomic strategy can be applied to the identification and quantitation of protein complex components in human cells grown under different conditions...
  82. ncbi request reprint The rapid activation of protein synthesis by growth hormone requires signaling through mTOR
    Amanda A Hayashi
    Institute of Food Nutrition and Human Health, Massey University, and Metabolism and Microbial Genomics Section, AgResearch Limited, Palmerston North, New Zealand
    Am J Physiol Endocrinol Metab 292:E1647-55. 2007
    ..These results demonstrate for the first time that mTORC1 plays a major role in the rapid activation of protein synthesis by GH...
  83. ncbi request reprint Signalling to translation: how signal transduction pathways control the protein synthetic machinery
    Christopher G Proud
    Department of Biochemistry and Molecular Biology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3
    Biochem J 403:217-34. 2007
    ..However, important questions remain about both the contributions of individual regulatory events to the control of general protein synthesis and the mechanisms by which the translation of specific mRNAs is controlled...
  84. ncbi request reprint Shut-down of translation, a global neuronal stress response: mechanisms and pathological relevance
    Wulf Paschen
    Multidisciplinary Neuroprotection Laboratories, Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA
    Curr Pharm Des 13:1887-902. 2007
    ....
  85. ncbi request reprint PRAS40 is a target for mammalian target of rapamycin complex 1 and is required for signaling downstream of this complex
    Bruno D Fonseca
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada
    J Biol Chem 282:24514-24. 2007
    ..However, this has no effect on the phosphorylation of Akt or TSC2 (an Akt substrate). These data place PRAS40 downstream of mTORC1 but upstream of its effectors, such as S6K1 and 4E-BP1...
  86. pmc Exercise rapidly increases eukaryotic elongation factor 2 phosphorylation in skeletal muscle of men
    Adam J Rose
    Copenhagen Muscle Research Centre, Institute of Exercise and Sport Sciences, Department of Human Physiology, Copenhagen University, Denmark
    J Physiol 569:223-8. 2005
    ..Given that eEF2 phosphorylation inhibits eEF2 activity and mRNA translation, these findings suggest that the inhibition of protein synthesis in contracting skeletal muscle is due to the Ca(2)(+)-induced stimulation of eEF2 kinase...