Peter J Parker
Affiliation: Cancer Research UK
- PKC at a glancePeter 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
- Detecting protein-phospholipid interactions. Epidermal growth factor-induced activation of phospholipase D1b in situWilliam 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...
- Receptor trafficking controls weak signal delivery: a strategy used by c-Met for STAT3 nuclear accumulationStephanie 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...
- PKC controls HGF-dependent c-Met traffic, signalling and cell migrationStephanie 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...
- Identification of PKCzetaII: an endogenous inhibitor of cell polarityScott 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...
- The tumour suppressor RASSF1A is a novel substrate of PKCSunil 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...
- PKCepsilon-mediated phosphorylation of vimentin controls integrin recycling and motilityJohanna 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...
- PKCalpha reduces the lipid kinase activity of the p110alpha/p85alpha PI3K through the phosphorylation of the catalytic subunitSzabolcs 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...
- A selective PIKfyve inhibitor blocks PtdIns(3,5)P(2) production and disrupts endomembrane transport and retroviral buddingHarold 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...
- Altered cleavage and localization of PINK1 to aggresomes in the presence of proteasomal stressMiratul 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...
- Differential activation of the PI 3-kinase effectors AKT/PKB and p70 S6 kinase by compound 48/80 is mediated by PKCalphaRichard 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...
- 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...
- Protein kinase C phosphorylation: an introductionPeter J Parker
Cancer Research UK, London Research Institute, UK
Methods Mol Biol 233:159-62. 2003
- Hyperosmotic-induced protein kinase N 1 activation in a vesicular compartment is dependent upon Rac1 and 3-phosphoinositide-dependent kinase 1Neil 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...
- Dephosphorylation of PKCdelta by protein phosphatase 2Ac and its inhibition by nucleotidesJyoti 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...
- Calmodulin controls organization of the actin cytoskeleton via regulation of phosphatidylinositol (4,5)-bisphosphate synthesis in Saccharomyces cerevisiaeSylvane 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...
- PKC epsilon controls the traffic of beta1 integrins in motile cellsJohanna 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...
- Site-directed perturbation of protein kinase C- integrin interaction blocks carcinoma cell chemotaxisMaddy 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...
- Phosphorylation is required for PMA- and cell-cycle-induced degradation of protein kinase CdeltaJyoti 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...
- Protein kinase C phosphorylates ribosomal protein S6 kinase betaII and regulates its subcellular localizationTaras 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...
- Intramolecular and intermolecular interactions of protein kinase B define its activation in vivoVéronique 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...
- Protein kinase C controls microtubule-based traffic but not proteasomal degradation of c-MetStephanie 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...
- Integrin-specific signaling pathways controlling focal adhesion formation and cell migrationZohreh Mostafavi-Pour
School of Biological Sciences, University of Manchester, Manchester M13 9PT, UK
J Cell Biol 161:155-67. 2003....
- PKCepsilon is a permissive link in integrin-dependent IFN-gamma signalling that facilitates JAK phosphorylation of STAT1Johanna 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...
- 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 macrophagesAntonio Castrillo
, Centro Mixto CSIC-UCM, Facultad de Farmacia, and Centro Nacional de Investigaciones Cardiovasculares, 28040 Madrid, Spain
Mol Cell Biol 23:1196-208. 2003....
- The identification and characterization of novel PKCepsilon phosphorylation sites provide evidence for functional cross-talk within the PKC superfamilyJoanne 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...
- The regulated assembly of a PKCepsilon complex controls the completion of cytokinesisAdrian 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...
- PIKfyve negatively regulates exocytosis in neurosecretory cellsShona 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...
- The scaffold MyD88 acts to couple protein kinase Cepsilon to Toll-like receptorsAmir 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...
- Novel phosphorylation site markers of protein kinase C delta activationJoanne 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...
- PKCzetaII is a target for degradation through the tumour suppressor protein pVHLXavier 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...
- PKC alpha protein but not kinase activity is critical for glioma cell proliferation and survivalAngus 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...
- Fab1p and AP-1 are required for trafficking of endogenously ubiquitylated cargoes to the vacuole lumen in S. cerevisiaeJohn 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...
- FGF-2 protects small cell lung cancer cells from apoptosis through a complex involving PKCepsilon, B-Raf and S6K2Olivier 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...
- The von Hippel-Lindau tumour-suppressor protein interaction with protein kinase CdeltaXavier 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...
- Prognostic value of an activation state marker for epidermal growth factor receptor in tissue microarrays of head and neck cancerAnthony 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...
- Phosphatidylinositol 3-kinase C2alpha is essential for ATP-dependent priming of neurosecretory granule exocytosisFrederic 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...
- Nucleotide binding by the Mdm2 RING domain facilitates Arf-independent Mdm2 nucleolar localizationMasha 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...
- Svp1p defines a family of phosphatidylinositol 3,5-bisphosphate effectorsStephen 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...
- PtdIns-specific MPR pathway association of a novel WD40 repeat protein, WIPI49Tim 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...
- Emerging and diverse roles of protein kinase C in immune cell signallingSeng-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...