P J Parker

Summary

Affiliation: Cancer Research UK
Country: UK

Publications

  1. pmc A selective PIKfyve inhibitor blocks PtdIns(3,5)P(2) production and disrupts endomembrane transport and retroviral budding
    Harold B J Jefferies
    London Research Institute Cancer Research UK, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    EMBO Rep 9:164-70. 2008
  2. pmc Receptor trafficking controls weak signal delivery: a strategy used by c-Met for STAT3 nuclear accumulation
    Stephanie Kermorgant
    Department of Tumour Biology, Cancer Research UK Clinical Centre, Bart s and the London Queen Mary s School of Medicine and Dentistry, London EC1M 6BQ, England, UK
    J Cell Biol 182:855-63. 2008
  3. pmc Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration
    Sylvie Lachmann
    Protein Phosphorylation Laboratory, London Research Institute, London, United Kingdom
    PLoS ONE 6:e21732. 2011
  4. pmc An aPKC-exocyst complex controls paxillin phosphorylation and migration through localised JNK1 activation
    Carine Rosse
    Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, London, United Kingdom
    PLoS Biol 7:e1000235. 2009
  5. pmc Regulation of polarized morphogenesis by protein kinase C iota in oncogenic epithelial spheroids
    Mark Linch
    Department of Protein Phosphorylation, Cancer Research UK London Research Institute, London WC2A 3LY, UK
    Carcinogenesis 35:396-406. 2014
  6. pmc 14-3-3 proteins interact with a hybrid prenyl-phosphorylation motif to inhibit G proteins
    Philippe Riou
    Randall Division of Cell and Molecular Biophysics, New Hunt s House, King s College London, London, UK
    Cell 153:640-53. 2013
  7. pmc PKC epsilon controls the traffic of beta1 integrins in motile cells
    Johanna Ivaska
    Protein Phosphorylation Laboratory and Electron Microscopy Unit, Cancer Research UK London Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, UK Corresponding author e mail
    EMBO J 21:3608-19. 2002
  8. ncbi request reprint The ubiquitous phosphoinositides
    P J Parker
    Protein Phosphorylation Laboratory, London Research Institute CRUK, 44 Lincoln s Inn Fields, London EC2A 3PX, UK
    Biochem Soc Trans 32:893-8. 2004
  9. ncbi request reprint p42 MAPK phosphorylates 80 kDa MARCKS at Ser-113
    D C Schönwasser
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, London, UK
    FEBS Lett 395:1-5. 1996
  10. ncbi request reprint Rapamycin-sensitive phosphorylation of PKC on a carboxy-terminal site by an atypical PKC complex
    W H Ziegler
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London, WC2A 3PX, UK
    Curr Biol 9:522-9. 1999

Detail Information

Publications88

  1. pmc A selective PIKfyve inhibitor blocks PtdIns(3,5)P(2) production and disrupts endomembrane transport and retroviral budding
    Harold B J Jefferies
    London Research Institute Cancer Research UK, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    EMBO Rep 9:164-70. 2008
    ..We concluded that the phosphatidylinositol 3,5-bisphosphate pathway is integral to endosome formation, determining morphology and cargo flux...
  2. pmc Receptor trafficking controls weak signal delivery: a strategy used by c-Met for STAT3 nuclear accumulation
    Stephanie Kermorgant
    Department of Tumour Biology, Cancer Research UK Clinical Centre, Bart s and the London Queen Mary s School of Medicine and Dentistry, London EC1M 6BQ, England, UK
    J Cell Biol 182:855-63. 2008
    ..This response is triggered from peripheral endosomes. Thus, control of growth factor receptor traffic determines the nature of the signal output, providing novel opportunities for intervention...
  3. pmc Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration
    Sylvie Lachmann
    Protein Phosphorylation Laboratory, London Research Institute, London, United Kingdom
    PLoS ONE 6:e21732. 2011
    ..It is concluded that intervention in PKNs may need to be directed at multiple isoforms to be effective in different cell types...
  4. pmc An aPKC-exocyst complex controls paxillin phosphorylation and migration through localised JNK1 activation
    Carine Rosse
    Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, London, United Kingdom
    PLoS Biol 7:e1000235. 2009
    ....
  5. pmc Regulation of polarized morphogenesis by protein kinase C iota in oncogenic epithelial spheroids
    Mark Linch
    Department of Protein Phosphorylation, Cancer Research UK London Research Institute, London WC2A 3LY, UK
    Carcinogenesis 35:396-406. 2014
    ..The identification of a PKCι inhibitor that can restore polarized morphogenesis has implications for the treatment of Ras and ErbB2 driven malignancies. ..
  6. pmc 14-3-3 proteins interact with a hybrid prenyl-phosphorylation motif to inhibit G proteins
    Philippe Riou
    Randall Division of Cell and Molecular Biophysics, New Hunt s House, King s College London, London, UK
    Cell 153:640-53. 2013
    ..In contrast to the canonical GTP/GDP switch that regulates most Ras superfamily members, our results reveal an unprecedented mechanism for G protein inhibition by 14-3-3 proteins...
  7. pmc PKC epsilon controls the traffic of beta1 integrins in motile cells
    Johanna Ivaska
    Protein Phosphorylation Laboratory and Electron Microscopy Unit, Cancer Research UK London Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, UK Corresponding author e mail
    EMBO J 21:3608-19. 2002
    ..The evidence presented indicates that PKC epsilon controls an internal traffic step that under uninhibited conditions permits the recycling of beta 1 integrin, contributing to cell motility...
  8. ncbi request reprint The ubiquitous phosphoinositides
    P J Parker
    Protein Phosphorylation Laboratory, London Research Institute CRUK, 44 Lincoln s Inn Fields, London EC2A 3PX, UK
    Biochem Soc Trans 32:893-8. 2004
    ..The metabolic map of this pathway and the nature of the binding partner interactions are reviewed...
  9. ncbi request reprint p42 MAPK phosphorylates 80 kDa MARCKS at Ser-113
    D C Schönwasser
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, London, UK
    FEBS Lett 395:1-5. 1996
    ..1994) J. Biol. Chem. 269, 18299-18302], its phosphorylation is not subject to acute regulation by p42 MAPK in Swiss 3T3 cells...
  10. ncbi request reprint Rapamycin-sensitive phosphorylation of PKC on a carboxy-terminal site by an atypical PKC complex
    W H Ziegler
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London, WC2A 3PX, UK
    Curr Biol 9:522-9. 1999
    ..Although this site is crucial to the control of this class of enzymes, the upstream kinase(s) has not been identified...
  11. ncbi request reprint SAC1 encodes a regulated lipid phosphoinositide phosphatase, defects in which can be suppressed by the homologous Inp52p and Inp53p phosphatases
    W E Hughes
    Protein Phosphorylation, Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    J Biol Chem 275:801-8. 2000
    ..It is concluded that SAC1 encodes a novel lipid phosphoinositide phosphatase in which specific mutations can cause the sac1 phenotypes by altering the in vivo regulation of the protein rather than by destroying phosphatase activity...
  12. ncbi request reprint 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...
  13. ncbi request reprint Rho GTPase control of protein kinase C-related protein kinase activation by 3-phosphoinositide-dependent protein kinase
    P Flynn
    Imperial Cancer Research Fund, Protein Phosphorylation Laboratory, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    J Biol Chem 275:11064-70. 2000
    ..Furthermore, this in vivo complex is maintained after phosphoinositide 3-kinase inhibition. The control of PRKs by PDK1 thus evidences a novel strategy of substrate-directed control involving GTPases...
  14. ncbi request reprint PRK1 phosphorylates MARCKS at the PKC sites: serine 152, serine 156 and serine 163
    R H Palmer
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, London, UK
    FEBS Lett 378:281-5. 1996
    ..The implications for MARCKS as a marker of PKC activation and as a point of signal convergence are discussed...
  15. pmc Sac phosphatase domain proteins
    W E Hughes
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, 44, Lincoln s Inn Fields, London WC2A 3PX, UK
    Biochem J 350:337-52. 2000
    ..This review describes the Sac phosphatase domain-containing proteins and their actions, with particular reference to the genetic and biochemical insights provided by study of the yeast Saccharomyces cerevisiae...
  16. ncbi request reprint PRK1 is targeted to endosomes by the small GTPase, RhoB
    H Mellor
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    J Biol Chem 273:4811-4. 1998
    ..Translocation of PRK1 to the endosomal compartment by RhoB is accompanied by a shift in the electrophoretic mobility of the kinase indicative of an accompanying activation...
  17. pmc The broad specificity of dominant inhibitory protein kinase C mutants infers a common step in phosphorylation
    P Garcia-Paramio
    Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Biochem J 333:631-6. 1998
    ..In the case of the PKCalpha mutant, it was shown that inhibition required the full-length mutant protein. The results provide evidence for the involvement of a common step in the phosphorylation of all PKC isotypes...
  18. ncbi request reprint Imaging protein kinase Calpha activation in cells
    T Ng
    Protein Phosphorylation Laboratory and Cell Biophysics Laboratory, Imperial Cancer Research Fund ICRF, 44 Lincoln s Inn Fields, London, WC2A 3PX, UK
    Science 283:2085-9. 1999
    ..This approach enabled the imaging of PKCalpha activation in live and fixed cultured cells and was also applied to pathological samples...
  19. ncbi request reprint Regulated binding of the protein kinase C substrate GAP-43 to the V0/C2 region of protein kinase C-delta
    L V Dekker
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    J Biol Chem 272:12747-53. 1997
    ..It is concluded that protein kinase C-delta interacts with GAP-43 through the V0/C2-like domain, outside the catalytic site, and that this interaction is modulated by intracellular Ca2+...
  20. ncbi request reprint c-Met signalling: spatio-temporal decisions
    S Kermorgant
    Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, London, UK
    Cell Cycle 4:352-5. 2005
    ..The mechanisms involved and the implications for signalling studies are discussed...
  21. ncbi request reprint Multiple interactions of PRK1 with RhoA. Functional assignment of the Hr1 repeat motif
    P Flynn
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    J Biol Chem 273:2698-705. 1998
    ..Additionally, it is observed that the V14RhoA mutant binds HR1a but does not bind HR1b. This distinct binding behavior corroborates the conclusion that there are independent contacts on RhoA for the HR1aPRK1 and HR1bPRK1 motifs...
  22. ncbi request reprint Crystal structure of the C2 domain from protein kinase C-delta
    H Pappa
    Structural Biology, Imperial Cancer Research Fund, London, UK
    Structure 6:885-94. 1998
    ..Biochemical data suggest that this domain serves to translocate novel PKC family members to the plasma membrane and may influence binding of PKC activators...
  23. ncbi request reprint Biochemical characterization of the free catalytic p110 alpha and the complexed heterodimeric p110 alpha.p85 alpha forms of the mammalian phosphatidylinositol 3-kinase
    R Woscholski
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, London, United Kingdom
    J Biol Chem 269:25067-72. 1994
    ..p110 alpha) caused this effect. This mode of regulation is discussed in the context of lipid kinase activation in vivo...
  24. ncbi request reprint Phosphorylation of protein kinase C-alpha on serine 657 controls the accumulation of active enzyme and contributes to its phosphatase-resistant state
    F Bornancin
    Imperial Cancer Research Fund, Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    J Biol Chem 272:3544-9. 1997
    ..These results are discussed in the context of a working model of PKCalpha behavior, providing insight into the workings of other kinases with equivalent sites of phosphorylation...
  25. ncbi request reprint Expression and characterization of protein kinase C-delta
    A R Olivier
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, London, England
    Eur J Biochem 200:805-10. 1991
    ..Like PKC-epsilon, PKC-delta displays no Ca2+ dependence for activation. The substrate specificity of PCK-delta is similar to that of PKC-epsilon but quite different from other PKCs...
  26. pmc Compartmental signal modulation: Endosomal phosphatidylinositol 3-phosphate controls endosome morphology and selective cargo sorting
    N Fili
    Cell Biophysics Laboratory and Protein Phosphorylation Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    Proc Natl Acad Sci U S A 103:15473-8. 2006
    ..The ability to acutely and selectively influence compartmental behavior as exemplified here for endomsomes clearly illustrates the power of the approach used to dissect the role of localized signals and events...
  27. ncbi request reprint Identification of the phosphorylated region responsible for the permissive activation of protein kinase C
    S M Cazaubon
    Imperial Cancer Research Fund, London, United Kingdom
    J Biol Chem 268:17559-63. 1993
    ..Coexpression of this PKC alpha mutant and wild type PKC beta demonstrates that the mutant has a dominant effect upon PKC beta phosphorylation. The location of this region and its phosphorylation in relation to PKC function are discussed...
  28. pmc Expression of mammalian protein kinase C in Schizosaccharomyces pombe: isotype-specific induction of growth arrest, vesicle formation, and endocytosis
    N T Goode
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, London, United Kingdom
    Mol Biol Cell 5:907-20. 1994
    ..Thus expression of specific mammalian PKC isotypes up-regulates endocytosis in S. pombe, providing a likely explanation for PKC-mediated receptor internalization in higher eukaryotes...
  29. ncbi request reprint Identification of multiple, novel, protein kinase C-related gene products
    R H Palmer
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, London, UK
    FEBS Lett 356:5-8. 1994
    ..The origin and relationships of these predicted proteins is discussed...
  30. ncbi request reprint Rho-dependence of Schizosaccharomyces pombe Pck2
    L G Sayers
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, London, UK
    Genes Cells 5:17-27. 2000
    ..The structural similarity between the Schizosaccaromyces pombe Pck proteins and the mammalian Rho-dependent protein kinase C-related family, has led us to investigate the relationship between the function of Rho and that of Pck1/2...
  31. ncbi request reprint Unique substrate specificity and regulatory properties of PKC-epsilon: a rationale for diversity
    D Schaap
    Ludwig Institute for Cancer Research, London, England
    FEBS Lett 243:351-7. 1989
    ..Subsequent analysis demonstrated that PKC-epsilon, while showing certain properties characteristic of the PKC family, has a quite distinct substrate specificity and is independent of Ca2+...
  32. ncbi request reprint Determination of the primary structure of PLC-154 demonstrates diversity of phosphoinositide-specific phospholipase C activities
    M Katan
    Ludwig Institute for Cancer Research, London, England
    Cell 54:171-7. 1988
    ..Regions of homology between PLC-154 and the previously described PLC-148 allow the assignment of a putative catalytic domain to the central region of PLC-154...
  33. pmc PKC controls HGF-dependent c-Met traffic, signalling and cell migration
    Stephanie Kermorgant
    Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, London, UK
    EMBO J 23:3721-34. 2004
    ..The dynamic properties conferred by the PKCepsilon control are shown to be essential for a normal HGF-dependent migratory response. Thus PKCs are shown to control both receptor traffic and signal traffic to relay HGF/c-Met responses...
  34. ncbi request reprint Cloning and expression patterns of two members of a novel protein-kinase-C-related kinase family
    R H Palmer
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, London, England
    Eur J Biochem 227:344-51. 1995
    ..PRK1 and PRK2, as well as a third member of this family, PRK3, show distinct patterns of expression in adult tissues...
  35. ncbi request reprint The stress-activated phosphatidylinositol 3-phosphate 5-kinase Fab1p is essential for vacuole function in S. cerevisiae
    F T Cooke
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, London, UK
    Curr Biol 8:1219-22. 1998
    ..Deletion of the FAB1 gene produces a loss of vacuolar morphology [6]; it is therefore concluded that PI(3,5)P2, the lipid product of Fab1p, is required for normal vacuolar function...
  36. ncbi request reprint Protein kinases, from B to C
    A J Cameron
    Protein Phosphorylation Lab, London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, U K
    Biochem Soc Trans 35:1013-7. 2007
    ..It is concluded that the distinct behaviours of PKB and PKC proteins are defined by the typical ground states of these proteins...
  37. ncbi request reprint Hyperosmotic-induced protein kinase N 1 activation in a vesicular compartment is dependent upon Rac1 and 3-phosphoinositide-dependent kinase 1
    Neil E Torbett
    Protein Phosphorylation Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    J Biol Chem 278:32344-51. 2003
    ..Taken together, our findings present a pathway for the selective hyperosmotic-induced Rac1-dependent PKN1 translocation and PDK1-dependent activation...
  38. doi request reprint PKC maturation is promoted by nucleotide pocket occupation independently of intrinsic kinase activity
    Angus J M Cameron
    Protein Phosphorylation Laboratory, Cancer Research UK, London Research Institute, London, UK
    Nat Struct Mol Biol 16:624-30. 2009
    ..These data demonstrate that autophosphorylation is not required for PKC priming and show how ATP pocket occupation can enable a kinase to mature as well as function...
  39. pmc Endosomal localization of phospholipase D 1a and 1b is defined by the C-termini of the proteins, and is independent of activity
    W E Hughes
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, 44, Lincoln s Inn Fields, London WC2A 3PX, UK
    Biochem J 356:727-36. 2001
    ....
  40. ncbi request reprint AGC protein kinase phosphorylation and protein kinase C
    P J Parker
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Biochem Soc Trans 29:860-3. 2001
    ..There are also distinctions relating to the turnover of these phosphorylations providing a further element of specificity...
  41. ncbi request reprint Differential activation of the PI 3-kinase effectors AKT/PKB and p70 S6 kinase by compound 48/80 is mediated by PKCalpha
    Richard D Byrne
    Division of Cell and Molecular Biology, Imperial College, London SW7 2AZ, United Kingdom
    Cell Signal 19:321-9. 2007
    ..The latter is only activated by higher doses of c48/80 resulting in an inhibition of the c48/80 induced PKB phosphorylation, thus explaining the observed biphasic activation profile for PKB in response to this secretagogue...
  42. ncbi request reprint Detecting protein-phospholipid interactions. Epidermal growth factor-induced activation of phospholipase D1b in situ
    William E Hughes
    Protein Phosphorylation Laboratory, Cancer Research United Kingdom London Research Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    J Biol Chem 277:22974-9. 2002
    ..Application of this approach will facilitate the spatial resolution of many protein-phospholipid interactions that are key events in the regulation of cellular processes...
  43. ncbi request reprint PKC at a glance
    Peter J Parker
    Protein Phosphorylation Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln s Inn Fields, London, WC2A 3PX, UK
    J Cell Sci 117:131-2. 2004
  44. pmc Role of a novel PH-kinase domain interface in PKB/Akt regulation: structural mechanism for allosteric inhibition
    Véronique Calleja
    Cell Biophysics Laboratory, Cancer Research UK
    PLoS Biol 7:e17. 2009
    ....
  45. ncbi request reprint Protein kinase C controls microtubule-based traffic but not proteasomal degradation of c-Met
    Stephanie Kermorgant
    Protein Phosphorylation Laboratory and Light Microscopy Laboratory, Cancer Research UK London Research Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, United Kingdom
    J Biol Chem 278:28921-9. 2003
    ..Thus susceptibility to proteasomal degradation is not a consequence of post-endocytic traffic. The data define a PKC-controlled traffic pathway for c-Met that operates independently of its degradative pathway...
  46. ncbi request reprint PKCepsilon is a permissive link in integrin-dependent IFN-gamma signalling that facilitates JAK phosphorylation of STAT1
    Johanna Ivaska
    Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Nat Cell Biol 5:363-9. 2003
    ..Thus, PKCepsilon functions as a central point of integration through which integrin engagement exerts a permissive input on IFN-gamma signalling...
  47. doi request reprint Manipulating signal delivery - plasma-membrane ERK activation in aPKC-dependent migration
    Katrina Boeckeler
    Protein Phosphorylation Laboratory, Cancer Research UK, London Research Institute, London, WC2A 3PX, UK
    J Cell Sci 123:2725-32. 2010
    ..The data further show that restored focal adhesion dynamics are a contributing mechanism through which localized ERK activity influences this aPKC-exocyst-dependent migration...
  48. ncbi request reprint Identification and characterisation of a novel splice variant of synaptojanin1
    R Woscholski
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, London, UK
    FEBS Lett 432:5-8. 1998
    ..However, the deletion of the SAC1 domain does not alter PtdInsP3 5-phosphatase activity demonstrating that the SAC1 domain is not necessary for catalytic function...
  49. ncbi request reprint Integrin-protein kinase C relationships
    J Ivaska
    Cancer Research UK, London Research Institute, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Biochem Soc Trans 31:90-3. 2003
    ..In the present paper, the developing understanding of the bi-directional relationship between the protein kinase C family of signal transducers and integrins is discussed...
  50. ncbi request reprint The activation of phosphatidylinositol 3-kinase by Ras
    T Kodaki
    Protein Phosphorylation Laboratory, Imperial Cancer Research Fund, London, UK
    Curr Biol 4:798-806. 1994
    ..Recent evidence indicates that Ras can bind to the p85 alpha/p110 alpha complex. We describe here the functional regulation of the mammalian phosphatidylinositol 3-kinase complex by Ras...
  51. doi request reprint PKC and the control of localized signal dynamics
    Carine Rosse
    Protein Phosphorylation Laboratory, London Research Institute Cancer Research UK, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Nat Rev Mol Cell Biol 11:103-12. 2010
    ..Examples of where and how various PKC isoforms direct this tier of signal organization are becoming more evident...
  52. pmc Conjugation of monoclonal antibodies to a synthetic peptide substrate for protein kinase: a method for labelling antibodies with 32P
    B M Foxwell
    Department of Cellular Pharmacology, Imperial Cancer Research Fund, London, UK
    Br J Cancer 57:489-93. 1988
    ..The application of this phosphorylation technique should allow the therapeutic potential of targeted 32P to be assessed...
  53. ncbi request reprint Differential regulation of glycogen synthase kinase-3 beta by protein kinase C isotypes
    N Goode
    Imperial Cancer Research Fund, Lincoln s Inn Fields, London, United Kingdom
    J Biol Chem 267:16878-82. 1992
    ..Phosphorylation of GSK-3 beta by PKC results in its specific inactivation. These results are consistent with a model in which activation of PKC stimulates c-Jun DNA binding by inhibiting its phosphorylation by GSK-3 beta...
  54. ncbi request reprint Biochemical properties of rat protein kinase C-eta expressed in COS cells
    L V Dekker
    Sandoz Institute for Medical Research, London, UK
    FEBS Lett 312:195-9. 1992
    ..Various PKC pseudosubstrate peptides are phosphorylated by PKC-eta in a phospholipid and TPA-dependent but calcium-independent manner. The polypeptide histone IIIS is a poor substrate...
  55. pmc Phosphorylation is required for PMA- and cell-cycle-induced degradation of protein kinase Cdelta
    Jyoti Srivastava
    Protein Phosphorylation Laboratory, Cancer Research UK London Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, U K
    Biochem J 368:349-55. 2002
    ..Analysis of phosphorylation-site mutants indicated that the T-loop Thr(505) phosphorylation site was critical for induced degradation...
  56. ncbi request reprint PKC alpha protein but not kinase activity is critical for glioma cell proliferation and survival
    Angus J Cameron
    Protein Phosphorylation Laboratory, Cancer Research UK, London Research Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, WC2A 3PX London, United Kingdom
    Int J Cancer 123:769-79. 2008
    ..These results indicate an essential pro-proliferative and pro-survival role for PKCalpha in glioma but question the use of ATP competitive inhibitors as therapeutics, either alone, or in combination with chemotoxic agents...
  57. ncbi request reprint Dephosphorylation of PKCdelta by protein phosphatase 2Ac and its inhibition by nucleotides
    Jyoti Srivastava
    Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, WC2A 3PX, London, UK
    FEBS Lett 516:265-9. 2002
    ..However the observation that binding of Mg-ATP to PKCdelta could protect the enzyme from dephosphorylation by PP2A(c) in vitro indicates that an additional input/factor is required for dephosphorylation in vivo...
  58. pmc Identification of PKCzetaII: an endogenous inhibitor of cell polarity
    Scott J Parkinson
    Protein Phosphorylation Laboratory, Cancer Research UK, London Research Institute, London, UK
    EMBO J 23:77-88. 2004
    ..The data demonstrate a regulatory role for PKCzetaII in the maintenance of cell transformation and the development of cell polarity...
  59. ncbi request reprint Identification, purification and characterization of a novel phosphatidylinositol-specific phospholipase C, a third member of the beta subfamily
    A J Carozzi
    Imperial Cancer Research Fund, Lincoln s Inn Fields, London, England
    Eur J Biochem 210:521-9. 1992
    ..min-1.mg-1, with PtdIns 4,5-bisphosphate as substrate. Substrate specificity and Ca2+ dependence of this purified PtdIns-PLC are characteristic of the PtdIns-PLC beta subfamily...
  60. ncbi request reprint A high-content, cell-based screen identifies micropolyin, a new inhibitor of microtubule dynamics
    Manu De Rycker
    Protein Phosphorylation Laboratory, London Research Institute, Cancer Research UK, London, UK
    Chem Biol Drug Des 73:599-610. 2009
    ..As our approach is unbiased, it should allow for discovery of new targets that may otherwise be overlooked...
  61. ncbi request reprint Novel phosphorylation site markers of protein kinase C delta activation
    Joanne Durgan
    Protein Phosphorylation Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln s Inn Fields, London, UK
    FEBS Lett 581:3377-81. 2007
    ..These data indicate that PKCdelta is phosphorylated upon activation and that phospho-S299 represents a useful marker of the activated enzyme...
  62. ncbi request reprint PKCzetaII is a target for degradation through the tumour suppressor protein pVHL
    Xavier Iturrioz
    Protein Phosphorylation Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln s Inn Fields Laboratories, London WC2A 3PX, UK
    FEBS Lett 581:1397-402. 2007
    ..The results indicate that pVHL recruits PKCzetaII via its PB1 domain and causes ubiquitination and degradation via the distal C-terminus of PKCzetaII...
  63. pmc PtdIns-specific MPR pathway association of a novel WD40 repeat protein, WIPI49
    Tim R Jeffries
    Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, Lincoln s Inn Fields Laboratories, London WC2A 3PX, United Kingdom
    Mol Biol Cell 15:2652-63. 2004
    ..We conclude that WIPI49 is a novel regulatory component of the endosomal and MPR pathway and that this role is dependent upon the PI-binding properties of its WD40 domain...
  64. pmc Phosphatidylinositol 3-kinase C2alpha is essential for ATP-dependent priming of neurosecretory granule exocytosis
    Frederic A Meunier
    Lincoln s Inn Fields Laboratories, London Research Institute, Cancer Research UK, London WC2A 3PX, United Kingdom
    Mol Biol Cell 16:4841-51. 2005
    ..Based on these results, we propose that production of PtdIns3P by PI3K-C2alpha is required for acquisition of fusion competence in neurosecretion...
  65. doi request reprint The identification and characterization of novel PKCepsilon phosphorylation sites provide evidence for functional cross-talk within the PKC superfamily
    Joanne Durgan
    Protein Phosphorylation Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Biochem J 411:319-31. 2008
    ..Thus our current findings identify three new phosphorylation sites that contribute to the isoform-specific function of PKCepsilon and highlight a novel and direct means of cross-talk between different members of the PKC superfamily...
  66. doi request reprint The scaffold MyD88 acts to couple protein kinase Cepsilon to Toll-like receptors
    Amir Faisal
    Protein Phosphorylation Laboratory, London Research Institute, Cancer Research UK, London WC2A 3PX, United Kingdom
    J Biol Chem 283:18591-600. 2008
    ..This study therefore identifies the scaffold protein MyD88 as the link coupling TLRs to PKCepsilon recruitment, phosphorylation, and downstream signaling...
  67. pmc Recognition of an intra-chain tandem 14-3-3 binding site within PKCepsilon
    Brenda Kostelecky
    Structural Biology Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    EMBO Rep 10:983-9. 2009
    ..This dual-site intra-chain recognition has implications for other 14-3-3 targets, which seem to have only a single 14-3-3 motif, as other lower affinity and cryptic 14-3-3 gatekeeper sites might exist...
  68. doi request reprint The regulated assembly of a PKCepsilon complex controls the completion of cytokinesis
    Adrian T Saurin
    Protein Phosphorylation Laboratory, London Research Institute, Cancer Research UK, London, WC2A 3PX, UK
    Nat Cell Biol 10:891-901. 2008
    ..This study therefore identifies a new regulatory mechanism that controls exit from cytokinesis, which has implications for carcinogenesis...
  69. pmc The von Hippel-Lindau tumour-suppressor protein interaction with protein kinase Cdelta
    Xavier Iturrioz
    Protein Phosphorylation Laboratory, Cancer Research UK London Research Institute, 44 Lincoln s Inn Fields, London, WC2A 3PX, UK
    Biochem J 397:109-20. 2006
    ..Thus, in contrast with aPKC, PKCdelta is not a conventional substrate of the ubiquitin-ligase complex, VCB-Cul-2, and the observed interaction between these two proteins must underlie a distinct signalling output...
  70. pmc Site-directed perturbation of protein kinase C- integrin interaction blocks carcinoma cell chemotaxis
    Maddy Parsons
    Richard Dimbleby Cancer Research UK Department of Cancer Research, GKT School of Medicine, St Thomas Hospital, London SE1 7EH, United Kingdom
    Mol Cell Biol 22:5897-911. 2002
    ..Importantly, our findings outline a new concept as to how carcinoma cell chemotaxis is enhanced and provide a conceptual basis for interfering with tumor cell dissemination...
  71. pmc Integrin-specific signaling pathways controlling focal adhesion formation and cell migration
    Zohreh Mostafavi-Pour
    School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK
    J Cell Biol 161:155-67. 2003
    ....
  72. pmc Potentiation of protein kinase C zeta activity by 15-deoxy-delta(12,14)-prostaglandin J(2) induces an imbalance between mitogen-activated protein kinases and NF-kappa B that promotes apoptosis in macrophages
    Antonio Castrillo
    Instituto de Bioquimica, Centro Mixto CSIC UCM, Facultad de Farmacia, and Centro Nacional de Investigaciones Cardiovasculares, 28040 Madrid, Spain
    Mol Cell Biol 23:1196-208. 2003
    ....
  73. 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...
  74. pmc Calmodulin controls organization of the actin cytoskeleton via regulation of phosphatidylinositol (4,5)-bisphosphate synthesis in Saccharomyces cerevisiae
    Sylvane Desrivieres
    Division of Biochemistry, Biozentrum, University of Basel, Klingelbergstrasse 70, Switzerland
    Biochem J 366:945-51. 2002
    ..Finally, the cmd1-226 mutant exhibits reduced levels of phosphatidylinositol (4,5)-bisphosphate. These findings suggest that calmodulin positively controls MSS4 activity and thereby the actin cytoskeleton...
  75. ncbi request reprint Protein kinase C phosphorylation: an introduction
    Peter J Parker
    Cancer Research UK, London Research Institute, UK
    Methods Mol Biol 233:159-62. 2003
  76. ncbi request reprint Molecular dissection of the interaction between the small G proteins Rac1 and RhoA and protein kinase C-related kinase 1 (PRK1)
    Darerca Owen
    Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, United Kingdom
    J Biol Chem 278:50578-87. 2003
    ..Surprisingly, as well as residues adjacent to Switch I, in Switch II, and in helix alpha5, it appears that the C-terminal stretch of basic amino acids in Rac is required for a high affinity interaction with HR1b...
  77. ncbi request reprint Altered cleavage and localization of PINK1 to aggresomes in the presence of proteasomal stress
    Miratul M K Muqit
    Department of Molecular Neuroscience, Institute of Neurology, University College London, London, UK
    J Neurochem 98:156-69. 2006
    ..These observations provide valuable insights into the mechanisms of LB formation in PD that should lead to a better understanding of PD pathogenesis...
  78. ncbi request reprint The tumour suppressor RASSF1A is a novel substrate of PKC
    Sunil K Verma
    Department of Medical Oncology, Medical Sciences Division, The University of Oxford, Oxford, UK
    FEBS Lett 582:2270-6. 2008
    ..By contrast, the equivalent AA mutant of RASSF1A phenocopied the WT protein. These findings indicate that PKC phosphorylation of RASSF1A regulates its ability to reorganize the microtubule network...
  79. pmc PKCepsilon-mediated phosphorylation of vimentin controls integrin recycling and motility
    Johanna Ivaska
    VTT Technical Research Centre for Finland, Medical Biotechnology and University of Turku Centre for Biotechnology, Turku, Finland
    EMBO J 24:3834-45. 2005
    ..Our results indicate that PKC-mediated phosphorylation of vimentin is a key process in integrin traffic through the cell...
  80. ncbi request reprint PKCalpha reduces the lipid kinase activity of the p110alpha/p85alpha PI3K through the phosphorylation of the catalytic subunit
    Szabolcs Sipeki
    Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry 9 Puskin St, Budapest, Hungary
    Biochem Biophys Res Commun 339:122-5. 2006
    ..We conclude that PKCalpha is able to modulate negatively the lipid kinase activity of the p110alpha/p85alpha PI3K through the phosphorylation of the catalytic subunit...
  81. pmc Intramolecular and intermolecular interactions of protein kinase B define its activation in vivo
    Véronique Calleja
    Cell Biophysics Laboratory, Lincoln s Inn Fields Laboratories, London Research Institute, Cancer Research UK, London, United Kingdom
    PLoS Biol 5:e95. 2007
    ..This has important implications not only in extending our understanding of this oncogenic protein kinase but also in opening up distinct opportunities for therapeutic intervention...
  82. ncbi request reprint Nucleotide binding by the Mdm2 RING domain facilitates Arf-independent Mdm2 nucleolar localization
    Masha V Poyurovsky
    Department of Biological Sciences, Columbia University, New York, NY 10027, USA
    Mol Cell 12:875-87. 2003
    ..We propose that nucleotide binding-facilitated nucleolar localization of Mdm2 is an evolutionarily conserved regulator of Mdm2 activity...
  83. ncbi request reprint Fab1p and AP-1 are required for trafficking of endogenously ubiquitylated cargoes to the vacuole lumen in S. cerevisiae
    John P Phelan
    Department of Biochemistry and Molecular Biology, University College London, Darwin Building, Gower Street, London, WC1E 6BT, UK
    J Cell Sci 119:4225-34. 2006
    ..Our data imply that AP-1 is required for some Fab1p and PtdIns(3,5)P2-dependent processes...
  84. ncbi request reprint Prognostic value of an activation state marker for epidermal growth factor receptor in tissue microarrays of head and neck cancer
    Anthony Kong
    Cell Biophysics Lab, London Research Institute, Cancer Research UK, London, UK
    Cancer Res 66:2834-43. 2006
    ..This powerful tool could be exploited as a new independent quantitative prognostic factor in clinical decisions and cancer management...
  85. ncbi request reprint PIKfyve negatively regulates exocytosis in neurosecretory cells
    Shona L Osborne
    Molecular Dynamics of Synaptic Function Laboratory, Queensland Brain Institute and School of Biomedical Sciences, University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia
    J Biol Chem 283:2804-13. 2008
    ..These results demonstrate a novel inhibitory role for PIKfyve catalytic activity in regulated secretion and provide further evidence for a fine tuning of exocytosis by 3-phosphorylated phosphoinositides...
  86. pmc Svp1p defines a family of phosphatidylinositol 3,5-bisphosphate effectors
    Stephen K Dove
    School of Biosciences, University of Birmingham, Birmingham, UK
    EMBO J 23:1922-33. 2004
    ..Svp1p is not involved in the contributions of FAB1/PtdIns(3,5)P2 to MVB sorting or to vacuole acidification and so additional PtdIns(3,5)P2 effectors must exist...
  87. pmc Emerging and diverse roles of protein kinase C in immune cell signalling
    Seng Lai Tan
    Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
    Biochem J 376:545-52. 2003
    ..The importance of PKCs in cellular immune responses suggests that improved understanding of the molecular events that govern their actions could point to new avenues for development of treatments for immune disorders...
  88. pmc FGF-2 protects small cell lung cancer cells from apoptosis through a complex involving PKCepsilon, B-Raf and S6K2
    Olivier E Pardo
    Lung Cancer Biology Group, Cancer Research UK, Imperial College London, Hammersmith Hospitals Campus, Du Cane Road, London, UK
    EMBO J 25:3078-88. 2006
    ..However, increased S6K1 kinase activity has no such effect. Thus, S6K2 but not S6K1 mediates prosurvival/chemoresistance signalling...