D R Alessi

Summary

Affiliation: University of Dundee
Country: UK

Publications

  1. ncbi Mechanism of activation and function of protein kinase B
    D R Alessi
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK
    Curr Opin Genet Dev 8:55-62. 1998
  2. ncbi Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha
    D R Alessi
    Medical Research Council Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee, DD1 4HN, Scotland
    Curr Biol 7:261-9. 1997
  3. ncbi 3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase
    D R Alessi
    Department of Biochemistry, University of Dundee, UK
    Curr Biol 7:776-89. 1997
  4. ncbi Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90(RSK) and cAMP-dependent protein kinase, but not its farnesylation at Cys(433), is essential for LKB1 to suppress cell vrowth
    G P Sapkota
    Medical Research Council Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland
    J Biol Chem 276:19469-82. 2001
  5. ncbi Further evidence that the inhibition of glycogen synthase kinase-3beta by IGF-1 is mediated by PDK1/PKB-induced phosphorylation of Ser-9 and not by dephosphorylation of Tyr-216
    M Shaw
    Department of Biochemistry, University of Dundee, UK
    FEBS Lett 416:307-11. 1997
  6. pmc Identification of pleckstrin-homology-domain-containing proteins with novel phosphoinositide-binding specificities
    S Dowler
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 351:19-31. 2000
  7. ncbi PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2
    A Balendran
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee DD1 5EH, UK
    Curr Biol 9:393-404. 1999
  8. ncbi Functional analysis of LKB1/STK11 mutants and two aberrant isoforms found in Peutz-Jeghers Syndrome patients
    J Boudeau
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland
    Hum Mutat 21:172. 2003
  9. pmc Crystal structure of the phosphatidylinositol 3,4-bisphosphate-binding pleckstrin homology (PH) domain of tandem PH-domain-containing protein 1 (TAPP1): molecular basis of lipid specificity
    C C Thomas
    Division of Biological Chemistry and Molecular Microbiology, Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 358:287-94. 2001
  10. ncbi The role of 3-phosphoinositide-dependent protein kinase 1 in activating AGC kinases defined in embryonic stem cells
    M R Williams
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dundee, DD1 5EH, Scotland
    Curr Biol 10:439-48. 2000

Collaborators

Detail Information

Publications45

  1. ncbi Mechanism of activation and function of protein kinase B
    D R Alessi
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK
    Curr Opin Genet Dev 8:55-62. 1998
    ..The highlights include the discovery of a protein kinase required for the 3-phosphoinositide-dependent activation of PKB and the identification of several physiological substrates for PKB...
  2. ncbi Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Balpha
    D R Alessi
    Medical Research Council Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee, DD1 4HN, Scotland
    Curr Biol 7:261-9. 1997
    ..The phosphorylation of both residues is required for maximal activation of PKB. The kinases that phosphorylate PKB are, however, unknown...
  3. ncbi 3-Phosphoinositide-dependent protein kinase-1 (PDK1): structural and functional homology with the Drosophila DSTPK61 kinase
    D R Alessi
    Department of Biochemistry, University of Dundee, UK
    Curr Biol 7:776-89. 1997
    ....
  4. ncbi Phosphorylation of the protein kinase mutated in Peutz-Jeghers cancer syndrome, LKB1/STK11, at Ser431 by p90(RSK) and cAMP-dependent protein kinase, but not its farnesylation at Cys(433), is essential for LKB1 to suppress cell vrowth
    G P Sapkota
    Medical Research Council Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland
    J Biol Chem 276:19469-82. 2001
    ..In contrast, a mutant of LKB1 that cannot be prenylated was still able to suppress the growth of cells...
  5. ncbi Further evidence that the inhibition of glycogen synthase kinase-3beta by IGF-1 is mediated by PDK1/PKB-induced phosphorylation of Ser-9 and not by dephosphorylation of Tyr-216
    M Shaw
    Department of Biochemistry, University of Dundee, UK
    FEBS Lett 416:307-11. 1997
    ..Coexpression of WT-GSK3beta in 293 cells with either PKB alpha (also known as AKT) or PDK1 (the 'upstream' activator of PKB) mimicked the IGF-1- or insulin-induced phosphorylation of Ser-9 and inactivation of GSK3beta...
  6. pmc Identification of pleckstrin-homology-domain-containing proteins with novel phosphoinositide-binding specificities
    S Dowler
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 351:19-31. 2000
    ..This study lays the foundation for future work to establish the phospholipid-binding specificities of these proteins in vivo, and their physiological role(s)...
  7. ncbi PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived from the carboxyl terminus of PRK2
    A Balendran
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee DD1 5EH, UK
    Curr Biol 9:393-404. 1999
    ..Thr308 is phosphorylated by the 3-phosphoinositide-dependent protein kinase-1 (PDK1) but the identity of the kinase that phosphorylates Ser473 (provisionally termed PDK2) is unknown...
  8. ncbi Functional analysis of LKB1/STK11 mutants and two aberrant isoforms found in Peutz-Jeghers Syndrome patients
    J Boudeau
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland
    Hum Mutat 21:172. 2003
    ....
  9. pmc Crystal structure of the phosphatidylinositol 3,4-bisphosphate-binding pleckstrin homology (PH) domain of tandem PH-domain-containing protein 1 (TAPP1): molecular basis of lipid specificity
    C C Thomas
    Division of Biological Chemistry and Molecular Microbiology, Wellcome Trust Biocentre, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 358:287-94. 2001
    ....
  10. ncbi The role of 3-phosphoinositide-dependent protein kinase 1 in activating AGC kinases defined in embryonic stem cells
    M R Williams
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dundee, DD1 5EH, Scotland
    Curr Biol 10:439-48. 2000
    ....
  11. ncbi A 3-phosphoinositide-dependent protein kinase-1 (PDK1) docking site is required for the phosphorylation of protein kinase Czeta (PKCzeta ) and PKC-related kinase 2 by PDK1
    A Balendran
    MRC Protein Phosphorylation Unit, Division of Signal Transduction Therapy, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    J Biol Chem 275:20806-13. 2000
    ..These findings indicate that the hydrophobic motif of PRK2 and PKCzeta acts as a "docking site" enabling the recruitment of PDK1 to these substrates. This is essential for their phosphorylation by PDK1 in cells...
  12. 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)...
  13. pmc Mechanism of activation of protein kinase B by insulin and IGF-1
    D R Alessi
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK
    EMBO J 15:6541-51. 1996
    ..We propose a model whereby PKBalpha becomes phosphorylated and activated in insulin/IGF-1-stimulated cells by an upstream kinase(s)...
  14. ncbi Evidence that 3-phosphoinositide-dependent protein kinase-1 mediates phosphorylation of p70 S6 kinase in vivo at Thr-412 as well as Thr-252
    A Balendran
    Medical Research Council Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee DD1 5EH, Scotland
    J Biol Chem 274:37400-6. 1999
    ..These observations indicate that PDK1 regulates the activation of p70 S6 kinase and provides evidence that PDK1 mediates the phosphorylation of p70 S6 kinase at Thr-412...
  15. pmc Role of phosphatidylinositol 3,4,5-trisphosphate in regulating the activity and localization of 3-phosphoinositide-dependent protein kinase-1
    R A Currie
    Department of Biochemistry, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U K
    Biochem J 337:575-83. 1999
    ..Thirdly, the interaction of PDK1 with PtdIns(3,4,5)P3 facilitates the rate at which it can activate PKB...
  16. pmc The PIF-binding pocket in PDK1 is essential for activation of S6K and SGK, but not PKB
    R M Biondi
    Division of Signal Transduction Therapy, MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    EMBO J 20:4380-90. 2001
    ..The PIF-binding pocket represents a substrate recognition site on a protein kinase that is only required for the phosphorylation of a subset of its physiological substrates...
  17. pmc Phosphoinositide 3-kinase-dependent phosphorylation of the dual adaptor for phosphotyrosine and 3-phosphoinositides by the Src family of tyrosine kinase
    S Dowler
    MRC Protein Phosphorylation Unit, Department of Biochemistry, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 349:605-10. 2000
    ..These findings indicate that, following activation of PI 3-kinases, PtdIns(3,4,5)P(3) or PtdIns(3,4)P(2) bind to DAPP1, recruiting it to the plasma membrane where it becomes phosphorylated at Tyr(139) by a Src-family tyrosine kinase...
  18. ncbi 3-Phosphoinositide-dependent protein kinase 1 (PDK1) phosphorylates and activates the p70 S6 kinase in vivo and in vitro
    D R Alessi
    Department of Biochemistry, MRC Phosphorylation Unit, University of Dundee, Dundee, UK
    Curr Biol 8:69-81. 1998
    ..It is not known which protein kinases phosphorylate and activate p70...
  19. pmc Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB
    M Deak
    MRC Protein Phosphorylation Unit, Departments of Biochemistry, Anatomy and Physiology, University of Dundee, Scotland
    EMBO J 17:4426-41. 1998
    ..These findings, together with other observations, suggest that MSK1 may mediate the growth-factor and stress-induced activation of CREB...
  20. pmc Identification of a pocket in the PDK1 kinase domain that interacts with PIF and the C-terminal residues of PKA
    R M Biondi
    Divison of Signal Transduction Therapy, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    EMBO J 19:979-88. 2000
    ..Our results suggest that the PIF-binding pocket on the kinase domain of PDK1 acts as a 'docking site', enabling it to interact with and enhance the phosphorylation of its substrates...
  21. pmc Phosphorylation of Ser-241 is essential for the activity of 3-phosphoinositide-dependent protein kinase-1: identification of five sites of phosphorylation in vivo
    A Casamayor
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee DD1 5EH, Scotland, U K
    Biochem J 342:287-92. 1999
    ..PDK1 expressed in bacteria was active and phosphorylated at Ser-241, suggesting that PDK1 can phosphorylate itself at this site, leading to its own activation...
  22. pmc The activation of protein kinase B by H2O2 or heat shock is mediated by phosphoinositide 3-kinase and not by mitogen-activated protein kinase-activated protein kinase-2
    M Shaw
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee DD1 4HN, UK
    Biochem J 336:241-6. 1998
    ..The activation of PKB isoforms by H2O2 may underlie some of the insulin-mimetic effects of this compound...
  23. pmc Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1
    D R Alessi
    Department of Biochemistry, University of Dundee, Scotland
    EMBO J 13:1610-9. 1994
    ....
  24. pmc DAPP1: a dual adaptor for phosphotyrosine and 3-phosphoinositides
    S Dowler
    MRC Protein Phosphorylation Unit, Department of Biochemistry, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U K
    Biochem J 342:7-12. 1999
    ....
  25. ncbi Characterisation of a plant 3-phosphoinositide-dependent protein kinase-1 homologue which contains a pleckstrin homology domain
    M Deak
    Department of Biochemistry, University of Dundee, UK
    FEBS Lett 451:220-6. 1999
    ..Arabidopsis 3-phosphoinositide-dependent protein kinase-1 is only the second plant protein reported to possess a pleckstrin homology domain and the first plant protein shown to bind 3-phosphoinositides...
  26. ncbi Discovery of PDK1, one of the missing links in insulin signal transduction. Colworth Medal Lecture
    D R Alessi
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, U K
    Biochem Soc Trans 29:1-14. 2001
    ..I will also discuss how these findings have enabled pharmaceutical companies to embark on novel programmes to develop improved therapies for the treatment of diabetes in the future...
  27. pmc Activation of protein kinase B beta and gamma isoforms by insulin in vivo and by 3-phosphoinositide-dependent protein kinase-1 in vitro: comparison with protein kinase B alpha
    K S Walker
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, Dundee DD1 4HN, Scotland, U K
    Biochem J 331:299-308. 1998
    ..Insulin did not induce PKBgamma activity in adipocytes, hepatocytes or skeletal muscle, but PKBgamma was the major isoform activated by insulin in rat L6 myotubes (a skeletal-muscle cell line)...
  28. pmc Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase
    L A Groom
    ICRF Molecular Pharmacology Unit, Ninewells Hospital, Dundee, UK
    EMBO J 15:3621-32. 1996
    ....
  29. ncbi Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
    D A Cross
    MRC Protein Phosphorylation Unit, Department of Biochemistry, University of Dundee, UK
    Nature 378:785-9. 1995
    ..Like the inhibition of GSK3 (refs 10, 14), the activation of PKB is prevented by inhibitors of phosphatidylinositol (PI) 3-kinase...
  30. ncbi Further evidence that 3-phosphoinositide-dependent protein kinase-1 (PDK1) is required for the stability and phosphorylation of protein kinase C (PKC) isoforms
    A Balendran
    MRC Protein Phosphorylation, MSI WTB complex, University of Dundee, Dow Street, DD1 5EH, Dundee, UK
    FEBS Lett 484:217-23. 2000
    ..In contrast, PRK2 is still partially phosphorylated at its T-loop in PDK1-/- cells, indicating the existence of a PDK1-independent mechanism for the phosphorylation of PRK2 at this residue...
  31. ncbi The human CL100 gene encodes a Tyr/Thr-protein phosphatase which potently and specifically inactivates MAP kinase and suppresses its activation by oncogenic ras in Xenopus oocyte extracts
    D R Alessi
    Department of Biochemistry, The University, Dundee
    Oncogene 8:2015-20. 1993
    ....
  32. ncbi PKB/Akt: a key mediator of cell proliferation, survival and insulin responses?
    M A Lawlor
    MRC Protein Phosphorylation Unit, Department of Life Sciences, University of Dundee, UK
    J Cell Sci 114:2903-10. 2001
    ..There are, however, a number of pitfalls of methodologies currently employed to study PKB function, and therefore caution should be used in interpretation of such experiments...
  33. pmc Phenformin as prophylaxis and therapy in breast cancer xenografts
    M V C L Appleyard
    Centre for Oncology and Molecular Medicine, University of Dundee, Dundee DD1 9SY, UK
    Br J Cancer 106:1117-22. 2012
    ..We also compared the efficacy of phenformin and metformin in the treatment of MDAMB231...
  34. pmc Effect of PI3K- and mTOR-specific inhibitors on spontaneous B-cell follicular lymphomas in PTEN/LKB1-deficient mice
    J M García-Martínez
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Br J Cancer 104:1116-25. 2011
    ..Here, we define the effectiveness of specific mTOR (AZD8055) and PI3K (GDC-0941) inhibitors, currently in clinical trials, in treating spontaneous B-cell follicular lymphoma that develops in PTEN(+/-)LKB1(+/hypo) mice...
  35. ncbi Molecular cloning of cDNA encoding the 110 kDa and 21 kDa regulatory subunits of smooth muscle protein phosphatase 1M
    Y H Chen
    Department of Biochemistry, University of Dundee, Scotland, UK
    FEBS Lett 356:51-5. 1994
    ..The M110 subunit is expressed in two different forms which differ in their C-terminal sequences. One of these is highly homologous to the whole of the M21 subunit...
  36. ncbi Regulation of glucose-6-phosphatase gene expression by protein kinase Balpha and the forkhead transcription factor FKHR. Evidence for insulin response unit-dependent and -independent effects of insulin on promoter activity
    D Schmoll
    Department of Biochemistry, Ernst Moritz Arndt University, D 17487 Greifswald, Germany
    J Biol Chem 275:36324-33. 2000
    ....
  37. pmc Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD
    A F Baas
    Hubrecht Laboratory, Centre for Biomedical Genetics, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands
    EMBO J 22:3062-72. 2003
    ..Removal of endogenous STRAD by siRNA abrogates the LKB1-induced G(1) arrest. Our results imply that STRAD plays a key role in regulating the tumour suppressor activities of LKB1...
  38. ncbi Mitogenic activation, phosphorylation, and nuclear translocation of protein kinase Bbeta
    R Meier
    Friedrich Miescher Institute, P O Box 2543, CH 4002 Basel, Switzerland
    J Biol Chem 272:30491-7. 1997
    ..These observations provide evidence that PKBbeta undergoes nuclear translocation upon mitogenic activation and support a role for PKB in signaling from receptor tyrosine kinases to the nucleus through phosphatidylinositol 3-kinase...
  39. ncbi Role of translocation in the activation and function of protein kinase B
    M Andjelkovic
    Friedrich Miescher Institut, Maulbeerstrasse 66, CH 4056 Basel, Switzerland
    J Biol Chem 272:31515-24. 1997
    ..Following activation the kinase detached from the membrane and translocated to the nucleus...
  40. ncbi Protein kinase C isotypes controlled by phosphoinositide 3-kinase through the protein kinase PDK1
    J A Le Good
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Science 281:2042-5. 1998
    ..The activation loop phosphorylation of PKCdelta in response to serum stimulation of cells was PI 3-kinase-dependent and was enhanced by PDK1 coexpression...
  41. ncbi Functional counterparts of mammalian protein kinases PDK1 and SGK in budding yeast
    A Casamayor
    MRC Protein Phosphorylation Unit Department of Biochemistry University of Dundee Dundee DD1 5EH Scotland UK
    Curr Biol 9:186-97. 1999
    ....
  42. ncbi Lithium inhibits caspase 3 activation and dephosphorylation of PKB and GSK3 induced by K+ deprivation in cerebellar granule cells
    A Mora
    , Facultad de Veterinaria, Universidad de Extremadura, Avenue Universidad s/n, , Spain
    J Neurochem 78:199-206. 2001
    ..Our results allow us to propose a new hypothesis about the action mechanism of lithium, this ion could inhibit a serine-threonine phosphatase induced by potassium deprivation...
  43. pmc The PI3K-PDK1 connection: more than just a road to PKB
    B Vanhaesebroeck
    Cell Signalling Group, Ludwig Institute for Cancer Research, 91 Riding House Street, London W1P 8BT, U K
    Biochem J 346:561-76. 2000
    ....
  44. ncbi A minimal cytoplasmic subdomain of the erythropoietin receptor mediates p70 S6 kinase phosphorylation
    M Y Zhang
    Department of Pediatrics, The Pennsylvania State University College of Medicine, The Milton S. Hershey Medical Center, Hershey, PA, USA
    Exp Hematol 29:432-40. 2001
    ..The results also demonstrate that PDK1 is a critical component in this signaling pathway, which requires the presence of domains between -131 and -221 for its activation of p70 S6K...
  45. ncbi Akt-mediated phosphorylation of the G protein-coupled receptor EDG-1 is required for endothelial cell chemotaxis
    M J Lee
    Center for Vascular Biology and Department of Physiology, University of Connecticut Health Center, Farmington, CT 06030, USA
    Mol Cell 8:693-704. 2001
    ..Transactivation of GPCRs by Akt may constitute a specificity switch to integrate rapid G protein-dependent signals into long-term cellular phenomena such as cell migration...