D R Alessi

Summary

Affiliation: University of Dundee
Country: UK

Publications

  1. ncbi Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade
    Simon A Hawley
    Division of Molecular Physiology, University of Dundee, Dundee DD1 5EH, UK
    J Biol 2:28. 2003
  2. ncbi New insights into mTOR signaling: mTORC2 and beyond
    Dario R Alessi
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD15EH, Scotland, UK
    Sci Signal 2:pe27. 2009
  3. ncbi Analysis of the LKB1-STRAD-MO25 complex
    Jerome Boudeau
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland
    J Cell Sci 117:6365-75. 2004
  4. 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
  5. ncbi LKB1-dependent signaling pathways
    Dario R Alessi
    Medical Research Council, Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland
    Annu Rev Biochem 75:137-63. 2006
  6. 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
  7. ncbi 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
  8. 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
  9. 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
  10. 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

Detail Information

Publications116 found, 100 shown here

  1. ncbi Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade
    Simon A Hawley
    Division of Molecular Physiology, University of Dundee, Dundee DD1 5EH, UK
    J Biol 2:28. 2003
    ..We recently showed that LKB1 exists as a complex with two accessory subunits, STRAD alpha/beta and MO25 alpha/beta...
  2. ncbi New insights into mTOR signaling: mTORC2 and beyond
    Dario R Alessi
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD15EH, Scotland, UK
    Sci Signal 2:pe27. 2009
    ..mTORC2 may control phosphorylation of the turn motif by promoting the activity of a kinase that targets the Ser/Thr-Pro sequence or by inhibiting the activity of a phosphatase...
  3. ncbi Analysis of the LKB1-STRAD-MO25 complex
    Jerome Boudeau
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland
    J Cell Sci 117:6365-75. 2004
    ..Taken together, our findings reinforce the functional importance of the binding of LKB1 to STRAD, and provide a greater understanding of the mechanism by which LKB1 is regulated and activated through its interaction with STRAD and MO25...
  4. 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...
  5. ncbi LKB1-dependent signaling pathways
    Dario R Alessi
    Medical Research Council, Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland
    Annu Rev Biochem 75:137-63. 2006
    ..The work described in this review shows how a study of an obscure cancer syndrome can uncover new and important regulatory pathways, relevant to the understanding of multiple human diseases...
  6. 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...
  7. ncbi 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)...
  8. 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...
  9. 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
    ....
  10. 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...
  11. 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
    ....
  12. 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
    ....
  13. ncbi LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1
    Jose M Lizcano
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee, UK
    EMBO J 23:833-43. 2004
    ..Between them, these kinases may mediate the physiological effects of LKB1, including its tumour suppressor function...
  14. ncbi 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
    ....
  15. 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...
  16. ncbi 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)...
  17. ncbi 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...
  18. ncbi ATP and MO25alpha regulate the conformational state of the STRADalpha pseudokinase and activation of the LKB1 tumour suppressor
    Elton Zeqiraj
    Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee, Scotland
    PLoS Biol 7:e1000126. 2009
    ..Thus, the function of STRADalpha is mediated through an active kinase conformation rather than kinase activity. It is possible that other pseudokinases exert their function through nucleotide binding and active conformations...
  19. ncbi 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. 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...
  21. 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
    ..PDK1 may, therefore, play a key role in mediating many of the actions of the second messenger(s) PtdIns(3,4, 5)P3 and/or PtdIns(3,4)P2...
  22. 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...
  23. ncbi 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...
  24. ncbi Role of T-loop phosphorylation in PDK1 activation, stability, and substrate binding
    David Komander
    Division of Biological Chemistry and Molecular Microbiology and MRC Protein Phosphorylation Unit, MSI WTB complex, School of Life Sciences, University of Dundee, Scotland
    J Biol Chem 280:18797-802. 2005
    ..These findings reveal that the integrity of the alpha C-helix and HM-pocket in PDK1 is not regulated by T-loop phosphorylation...
  25. ncbi 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...
  26. ncbi 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...
  27. ncbi Crystal structure of the PTPL1/FAP-1 human tyrosine phosphatase mutated in colorectal cancer: evidence for a second phosphotyrosine substrate recognition pocket
    Fabrizio Villa
    Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, DD1 5EH, Scotland
    J Biol Chem 280:8180-7. 2005
    ..Our studies provide the first molecular description of the PTPL1 catalytic domain and give new insight into the function of PTPL1...
  28. ncbi 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)...
  29. ncbi 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...
  30. ncbi 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...
  31. ncbi Control of AMPK-related kinases by USP9X and atypical Lys(29)/Lys(33)-linked polyubiquitin chains
    Abdallah K Al-Hakim
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 411:249-60. 2008
    ..The results of the present study demonstrate that NUAK1 and MARK4 are substrates of USP9X and provide the first evidence that AMPK family kinases are regulated by unusual Lys(29)/Lys(33)-linked polyubiquitin chains...
  32. ncbi Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation
    Elton Zeqiraj
    Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland
    Science 326:1707-11. 2009
    ..The structure also reveals how mutations found in Peutz-Jeghers syndrome and in various sporadic cancers impair LKB1 function...
  33. ncbi Role of the PDK1-PKB-GSK3 pathway in regulating glycogen synthase and glucose uptake in the heart
    Alfonso Mora
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland
    FEBS Lett 579:3632-8. 2005
    ....
  34. ncbi Use of Akt inhibitor and a drug-resistant mutant validates a critical role for protein kinase B/Akt in the insulin-dependent regulation of glucose and system A amino acid uptake
    Charlotte J Green
    Division of Molecular Physiology, James Black Centre, College of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    J Biol Chem 283:27653-67. 2008
    ....
  35. ncbi 14-3-3 binding to LRRK2 is disrupted by multiple Parkinson's disease-associated mutations and regulates cytoplasmic localization
    R Jeremy Nichols
    University of Dundee, Scotland, UK
    Biochem J 430:393-404. 2010
    ..These results provide the first evidence suggesting that 14-3-3 regulates LRRK2 and that disruption of the interaction of LRRK2 with 14-3-3 may be linked to Parkinson's disease...
  36. ncbi Regulation of activity and localization of the WNK1 protein kinase by hyperosmotic stress
    Anna Zagorska
    Medical Research Council Protein Phosphorylation Unit, School of Life Sciences, Medical Sciences Institute Wellcome Trust Biocentre Complex, University of Dundee, Dundee DD1 5EH, Scotland, UK
    J Cell Biol 176:89-100. 2007
    ..Mutational analysis suggests that the WNK1 C-terminal noncatalytic domain mediates vesicle localization. Our observations shed light on the mechanism by which WNK1 is regulated by hyperosmotic stress...
  37. 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...
  38. ncbi 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)...
  39. ncbi Role of the WNK-activated SPAK kinase in regulating blood pressure
    Fatema H Rafiqi
    University of Dundee, Scotland, UK
    EMBO Mol Med 2:63-75. 2010
    ..See accompanying Closeup by Maria Castañeda-Bueno and Gerald Gamba (DOI 10.1002/emmm.200900059)...
  40. ncbi Role that phosphorylation of GSK3 plays in insulin and Wnt signalling defined by knockin analysis
    Edward J McManus
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dundee, Scotland
    EMBO J 24:1571-83. 2005
    ..These results establish the function of Ser21/Ser9 phosphorylation in several processes in which GSK3 inactivation has previously been implicated...
  41. ncbi Regulation of the polarity kinases PAR-1/MARK by 14-3-3 interaction and phosphorylation
    Olga Göransson
    University of Dundee, MRC Protein Phosphorylation Unit, James Black Centre, Dow Street, Dundee, DD1 5EH, Scotland, UK
    J Cell Sci 119:4059-70. 2006
    ..Collectively, these results indicate that 14-3-3 binding to MARK isoforms is mediated by multiple phosphorylation sites, and serves to anchor MARK isoforms in the cytoplasm...
  42. ncbi 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
    ....
  43. ncbi 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
    ....
  44. 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...
  45. 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...
  46. ncbi Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)
    Juan M García-Martínez
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD15EH, Scotland, UK
    Biochem J 421:29-42. 2009
    ..Our results indicate that Ku-0063794 will be useful in delineating the physiological roles of mTOR and may have utility in treatment of cancers in which this pathway is inappropriately activated...
  47. ncbi BI-D1870 is a specific inhibitor of the p90 RSK (ribosomal S6 kinase) isoforms in vitro and in vivo
    Gopal P Sapkota
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U K
    Biochem J 401:29-38. 2007
    ....
  48. ncbi Inhibition of LRRK2 kinase activity leads to dephosphorylation of Ser(910)/Ser(935), disruption of 14-3-3 binding and altered cytoplasmic localization
    Nicolas Dzamko
    University of Dundee, Scotland, UK
    Biochem J 430:405-13. 2010
    ..They will also stimulate further research to understand how phosphorylation of Ser910 and Ser935 is controlled by LRRK2, and establish any relationship to development of Parkinson's disease...
  49. ncbi Deficiency of PDK1 in cardiac muscle results in heart failure and increased sensitivity to hypoxia
    Alfonso Mora
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    EMBO J 22:4666-76. 2003
    ..They also suggest that a deficiency of the PDK1 pathway might contribute to development of cardiac disease in humans...
  50. ncbi Structural insights into the recognition of substrates and activators by the OSR1 kinase
    Fabrizio Villa
    Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    EMBO Rep 8:839-45. 2007
    ..These results provide the first molecular insight into the mechanism by which the SPAK and OSR1 kinases specifically recognize their upstream activators and downstream substrates...
  51. ncbi Structural insights into the regulation of PDK1 by phosphoinositides and inositol phosphates
    David Komander
    Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee, Scotland, UK
    EMBO J 23:3918-28. 2004
    ....
  52. ncbi Crystal structure of MO25 alpha in complex with the C terminus of the pseudo kinase STE20-related adaptor
    Christine C Milburn
    Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland
    Nat Struct Mol Biol 11:193-200. 2004
    ....
  53. 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...
  54. 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...
  55. ncbi Regulation of Akt/PKB Ser473 phosphorylation
    Jose R Bayascas
    School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland
    Mol Cell 18:143-5. 2005
    ..In the past month, papers in a recent issue of Molecular Cell (Gao et al., 2005) and in Science (Sarbassov et al., 2005) may have identified the phosphatase and kinase acting on this residue...
  56. ncbi Mutation of the PDK1 PH domain inhibits protein kinase B/Akt, leading to small size and insulin resistance
    Jose R Bayascas
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland
    Mol Cell Biol 28:3258-72. 2008
    ..Our findings reveal how reduced activation of PKB isoforms impinges on downstream signaling pathways, causing diminution of size as well as insulin resistance...
  57. ncbi Binding of phosphatidylinositol 3,4,5-trisphosphate to the pleckstrin homology domain of protein kinase B induces a conformational change
    Christine C Milburn
    Division of Biological Chemistry and Molecular Microbiology, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Biochem J 375:531-8. 2003
    ..Our data provides the first structural insight into the mechanism by which the interaction of PKB with PtdIns(3,4,5)P3/PtdIns(3,4)P2 induces conformational changes that could enable PKB to be activated by PDK1...
  58. ncbi New roles for the LKB1-NUAK pathway in controlling myosin phosphatase complexes and cell adhesion
    Anna Zagorska
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Sci Signal 3:ra25. 2010
    ..Thus, LKB1 can influence the phosphorylation of targets not only through the AMPK family of kinases but also by controlling phosphatase complexes...
  59. ncbi High resolution crystal structure of the human PDK1 catalytic domain defines the regulatory phosphopeptide docking site
    Ricardo M Biondi
    Division of Signal Transduction Therapy, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    EMBO J 21:4219-28. 2002
    ..We discuss the possibility that an analogous phosphate-binding regulatory motif may participate in the activation of other AGC kinases. Furthermore, the structure of PDK1 provides a scaffold for the design of specific PDK1 inhibitors...
  60. ncbi PDK1, the master regulator of AGC kinase signal transduction
    Alfonso Mora
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Semin Cell Dev Biol 15:161-70. 2004
    ..We also discuss whether inhibitors of PDK1 might have chemotherapeutic potential in the treatment of cancers in which the PDK1-regulated AGC kinases are constitutively activated...
  61. ncbi Interactions of LY333531 and other bisindolyl maleimide inhibitors with PDK1
    David Komander
    Division of Biological Chemistry and Molecular Microbiology, University of Dundee, Dundee DD1 5EH, Scotland
    Structure 12:215-26. 2004
    ..A combination of site-directed mutagenesis and essential dynamics analysis gives further insight into PDK1 and also PKC inhibition by these compounds, and may aid inhibitor design...
  62. ncbi 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
    ....
  63. ncbi Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR
    Kei Sakamoto
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Scotland, UK
    Am J Physiol Endocrinol Metab 287:E310-7. 2004
    ..They also suggest that the effects of excercise, phenformin, and AICAR on metabolic processes in muscle may be mediated through activation of AMPK rather than activation of LKB1 or the AMPK-related kinases...
  64. ncbi Functional interactions of the SPAK/OSR1 kinases with their upstream activator WNK1 and downstream substrate NKCC1
    Alberto C Vitari
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 397:223-31. 2006
    ..These data establish that the CCT domain functions as a multipurpose docking site, enabling SPAK/OSR1 to interact with substrates (NKCC1) and activators (WNK1/WNK4)...
  65. ncbi The ubiquitin-associated domain of AMPK-related kinases regulates conformation and LKB1-mediated phosphorylation and activation
    Mahaboobi Jaleel
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 394:545-55. 2006
    ..Taken together, these findings suggest that the UBA domains of AMPK-related kinases play an important role in regulating the conformation, activation and localization of these enzymes...
  66. ncbi Insulin-induced Drosophila S6 kinase activation requires phosphoinositide 3-kinase and protein kinase B
    Jose M Lizcano
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 374:297-306. 2003
    ..The results of the present study support the view that, in Drosophila cells, dPI3K and dPKB, as well dTOR, are required for the activation of dS6K by insulin...
  67. ncbi Important role of the LKB1-AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice
    Xu Huang
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Biochem J 412:211-21. 2008
    ....
  68. ncbi Emerging roles of pseudokinases
    Jerome Boudeau
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Trends Cell Biol 16:443-52. 2006
    ..We also discuss the emerging functions of other pseudokinases, including HER3 (also called ErbB3), EphB6, CCK4 (also called PTK7), KSR, Trb3, GCN2, TRRAP, ILK and CASK...
  69. ncbi Substrate specificity and inhibitors of LRRK2, a protein kinase mutated in Parkinson's disease
    R Jeremy Nichols
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 424:47-60. 2009
    ..The findings of the present study will aid with the investigation of LRRK2...
  70. ncbi Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1)
    Laura R Pearce
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee, Scotland, U K
    Biochem J 431:245-55. 2010
    ..PF-4708671 is the first S6K1-specific inhibitor to be reported and will be a useful tool for delineating S6K1-specific roles downstream of mTOR...
  71. ncbi Ionizing radiation induces ataxia telangiectasia mutated kinase (ATM)-mediated phosphorylation of LKB1/STK11 at Thr-366
    Gopal P Sapkota
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U K
    Biochem J 368:507-16. 2002
    ..These observations provide the first link between ATM and LKB1 and suggest that ATM could regulate LKB1...
  72. ncbi Activation of the thiazide-sensitive Na+-Cl- cotransporter by the WNK-regulated kinases SPAK and OSR1
    Ciaran Richardson
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee, DD1 5EH, UK
    J Cell Sci 121:675-84. 2008
    ..They also suggest a mechanism by which increased WNK1 overexpression could lead to hypertension and that inhibitors of SPAK/OSR1 might be of use in reducing blood pressure by suppressing phosphorylation and hence activity of NCC...
  73. ncbi Role of TAPP1 and TAPP2 adaptor binding to PtdIns(3,4)P2 in regulating insulin sensitivity defined by knock-in analysis
    Stephan Wullschleger
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Biochem J 434:265-74. 2011
    ..These observations provide the first genetic evidence to support the notion that binding of TAPP1 and TAPP2 adap-tors to PtdIns(3,4)P(2) function as negative regulators of the insulin and PI3K signalling pathways...
  74. ncbi Identification of Protor as a novel Rictor-binding component of mTOR complex-2
    Laura R Pearce
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dundee DD1 5EH, Scotland, UK
    Biochem J 405:513-22. 2007
    ..Protor-1 is a novel Rictor-binding subunit of mTORC2, but further work is required to establish its role...
  75. ncbi Regulation of the NKCC2 ion cotransporter by SPAK-OSR1-dependent and -independent pathways
    Ciaran Richardson
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    J Cell Sci 124:789-800. 2011
    ....
  76. ncbi 14-3-3 cooperates with LKB1 to regulate the activity and localization of QSK and SIK
    Abdallah K Al-Hakim
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee, DD1 5EH, UK
    J Cell Sci 118:5661-73. 2005
    ..To our knowledge, this study provides the first example of 14-3-3 binding directly to the T-loop of a protein kinase and influencing its catalytic activity and cellular localization...
  77. ncbi Small-molecule inhibitors of PDK1
    Christian Peifer
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street Dundee DD15EH, Scotland, UK
    ChemMedChem 3:1810-38. 2008
    ..Herein we present for the first time a comprehensive collection of small molecules reported to interact with PDK1, and we refer to their biological characterisation in terms of activity and selectivity for PDK1...
  78. ncbi Identification and characterization of four novel phosphorylation sites (Ser31, Ser325, Thr336 and Thr366) on LKB1/STK11, the protein kinase mutated in Peutz-Jeghers cancer syndrome
    Gopal P Sapkota
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 362:481-90. 2002
    ....
  79. ncbi Cancer, oncogenes and signal transduction
    Edward J McManus
    Medical Research Council Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    Genome Biol 5:332. 2004
  80. ncbi Deficiency of PDK1 in liver results in glucose intolerance, impairment of insulin-regulated gene expression and liver failure
    Alfonso Mora
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 385:639-48. 2005
    ..They suggest that a deficiency of the PDK1 pathway in the liver could contribute to development of diabetes, as well as to liver failure...
  81. ncbi Evidence that the tandem-pleckstrin-homology-domain-containing protein TAPP1 interacts with Ptd(3,4)P2 and the multi-PDZ-domain-containing protein MUPP1 in vivo
    Wendy A Kimber
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 361:525-36. 2002
    ....
  82. ncbi WNK1, the kinase mutated in an inherited high-blood-pressure syndrome, is a novel PKB (protein kinase B)/Akt substrate
    Alberto C Vitari
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 378:257-68. 2004
    ..These results provide the first connection between the PI 3-kinase/PKB pathway and WNK1, suggesting a mechanism by which this pathway may influence blood pressure...
  83. ncbi Molecular basis for the substrate specificity of NIMA-related kinase-6 (NEK6). Evidence that NEK6 does not phosphorylate the hydrophobic motif of ribosomal S6 protein kinase and serum- and glucocorticoid-induced protein kinase in vivo
    Jose M Lizcano
    Medical Research Council Protein Phosphorylation Unit, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, United Kingdom
    J Biol Chem 277:27839-49. 2002
    ....
  84. ncbi Identification of the sucrose non-fermenting related kinase SNRK, as a novel LKB1 substrate
    Mahaboobi Jaleel
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    FEBS Lett 579:1417-23. 2005
    ..These results provide evidence that SNRK could mediate some of the physiological effects of LKB1...
  85. ncbi Hypomorphic mutation of PDK1 suppresses tumorigenesis in PTEN(+/-) mice
    Jose R Bayascas
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    Curr Biol 15:1839-46. 2005
    ....
  86. ncbi Interaction of the protein tyrosine phosphatase PTPL1 with the PtdIns(3,4)P2-binding adaptor protein TAPP1
    Wendy A Kimber
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 376:525-35. 2003
    ..Consistent with this notion we observed RNA-interference-mediated knock-down of TAPP1 in HEK-293 cells, enhanced activation and phosphorylation of PKB following IGF1 stimulation...
  87. ncbi Essential role of PDK1 in regulating cell size and development in mice
    Margaret A Lawlor
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    EMBO J 21:3728-38. 2002
    ..We provide genetic evidence that PDK1 is essential for mouse embryonic development, and regulates cell size independently of cell number or proliferation, as well as insulin's ability to activate PKB, S6K and RSK...
  88. ncbi Metformin and reduced risk of cancer in diabetic patients
    Josie M M Evans
    Division of Community Health Sciences, Section of Public Health, University of Dundee, Dundee DD2 4BF
    BMJ 330:1304-5. 2005
  89. ncbi The in vivo role of PtdIns(3,4,5)P3 binding to PDK1 PH domain defined by knockin mutation
    Edward J McManus
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dundee, UK
    EMBO J 23:2071-82. 2004
    ..These experiments establish the roles of the PDK1 regulatory domains and illustrate the power of knockin technology to probe the physiological function of protein-lipid and protein-protein interactions...
  90. ncbi The WNK1 and WNK4 protein kinases that are mutated in Gordon's hypertension syndrome phosphorylate and activate SPAK and OSR1 protein kinases
    Alberto C Vitari
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 391:17-24. 2005
    ..Our analysis also describes the first facile assay that can be employed to quantitatively assess WNK1 and WNK4 activity...
  91. ncbi In vivo role of the PIF-binding docking site of PDK1 defined by knock-in mutation
    Barry J Collins
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    EMBO J 22:4202-11. 2003
    ..They also illustrate the power of knock-in technology to probe the physiological roles of docking interactions in regulating the specificity of signal transduction pathways...
  92. ncbi Novel role for the LKB1 pathway in controlling monocarboxylate fuel transporters
    Beatrice Maria Filippi
    Medical Research Council Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK
    J Cell Biol 183:7-9. 2008
    ..This enables cells to import additional energy sources such as lactate and butyrate, enhancing the repertoire of fuels they can use to power vital activities...
  93. ncbi Heat-shock protein 90 and Cdc37 interact with LKB1 and regulate its stability
    Jerome Boudeau
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 370:849-57. 2003
    ..Hsp90 inhibitors are being considered as potential anti-cancer agents. However, our observations indicate that prolonged usage of these drugs could possibly lead to tumour development by decreasing cellular levels of LKB1...
  94. ncbi Evaluation of approaches to generation of tissue-specific knock-in mice
    Jose R Bayascas
    MRC Protein Phosphorylation Unit and School of Life Sciences, University of Dundee, Dundee DD1 5EH, United Kingdom
    J Biol Chem 281:28772-81. 2006
    ..We discuss the merits and disadvantages of each of the conditional knock-in approaches, along with the applications for which they may be most suited, and suggest how they could be further refined...
  95. ncbi MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm
    Jerome Boudeau
    MRC Protein Phosphorylation Unit, School of Life Sciences, MSI WTB complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    EMBO J 22:5102-14. 2003
    ..Our results indicate that MO25 may function as a scaffolding component of the LKB1-STRAD complex and plays a crucial role in regulating LKB1 activity and cellular localization...
  96. ncbi The nuts and bolts of AGC protein kinases
    Laura R Pearce
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee DD1 5EH, UK
    Nat Rev Mol Cell Biol 11:9-22. 2010
    ..In addition, AGC kinases mediate diverse and important cellular functions, and their mutation and/or dysregulation contributes to the pathogenesis of many human diseases, including cancer and diabetes...
  97. ncbi Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction
    Kei Sakamoto
    MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    EMBO J 24:1810-20. 2005
    ..These studies establish the importance of LKB1 in regulating AMPK activity and cellular energy levels in response to contraction and phenformin...
  98. ncbi In vivo role of the phosphate groove of PDK1 defined by knockin mutation
    Barry J Collins
    MRC Protein Phosphorylation Unit, MSI WTB complex, University of Dundee, Dundee, DD1 5EH, UK
    J Cell Sci 118:5023-34. 2005
    ..5-E11.5. The knockin embryos are observed until E19.5 and displayed general growth retardation and craniofacial developmental defects...
  99. ncbi mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)
    Juan M García-Martínez
    MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, UK
    Biochem J 416:375-85. 2008
    ..The results of the present study indicate that NDRG1 phosphorylation represents an excellent biomarker for mTORC2 activity...
  100. ncbi The regulation of salt transport and blood pressure by the WNK-SPAK/OSR1 signalling pathway
    Ciaran Richardson
    MRC Protein Phosphorylation Unit, Sir James Black Centre, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK
    J Cell Sci 121:3293-304. 2008
    ..We also discuss unresolved and controversial questions in this field of research...