Victor L J Tybulewicz

Summary

Affiliation: National Institute for Medical Research
Country: UK

Publications

  1. ncbi Vav-family proteins in T-cell signalling
    Victor L J Tybulewicz
    Division of Immune Cell Biology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Curr Opin Immunol 17:267-74. 2005
  2. doi Activation of the small GTPase Rac2 via the B cell receptor regulates B cell adhesion and immunological-synapse formation
    Eloisa Arana
    Lymphocyte Interaction Laboratory, Cancer Research UK, London Research Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Immunity 28:88-99. 2008
  3. pmc Down syndrome: searching for the genetic culprits
    Eva Lana-Elola
    MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK
    Dis Model Mech 4:586-95. 2011
  4. pmc Vav1 transduces T cell receptor signals to the activation of phospholipase C-gamma1 via phosphoinositide 3-kinase-dependent and -independent pathways
    Lucinda F Reynolds
    National Institute for Medical Research, London NW7 1AA, United Kingdom
    J Exp Med 195:1103-14. 2002
  5. pmc Crucial structural role for the PH and C1 domains of the Vav1 exchange factor
    Jonathan Rapley
    Division of Molecular Structure, and National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
    EMBO Rep 9:655-61. 2008
  6. pmc Mechanism and function of Vav1 localisation in TCR signalling
    Olga Ksionda
    Division of Immune Cell Biology, MRC National Institute for Medical Research, London NW7 1AA, UK
    J Cell Sci 125:5302-14. 2012
  7. pmc A novel Rac-dependent checkpoint in B cell development controls entry into the splenic white pulp and cell survival
    Robert B Henderson
    Division of Immune Cell Biology, Medical Research Council National Institute for Medical Research, London NW7 1AA, England, UK
    J Exp Med 207:837-53. 2010
  8. pmc An additional human chromosome 21 causes suppression of neural fate of pluripotent mouse embryonic stem cells in a teratoma model
    Afua Mensah
    Centre for Haematology, Institute of Cell and Molecular Science, Barts and The London, Queen Mary s School of Medicine, University of London, 4 Newark Street, London E1 2AT, UK
    BMC Dev Biol 7:131. 2007
  9. ncbi Commentary: New insights into the complexity of phosphatidylinositol lipid signaling in B lymphocytes
    Victor L J Tybulewicz
    Division of Immune Cell Biology, National Institute for Medical Research, London, UK
    Eur J Immunol 34:2964-7. 2004
  10. ncbi New techniques to understand chromosome dosage: mouse models of aneuploidy
    Victor L J Tybulewicz
    Division of Immune Cell Biology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
    Hum Mol Genet 15:R103-9. 2006

Collaborators

Detail Information

Publications55

  1. ncbi Vav-family proteins in T-cell signalling
    Victor L J Tybulewicz
    Division of Immune Cell Biology, National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Curr Opin Immunol 17:267-74. 2005
    ..An emerging theme is that Vav proteins may have important functions downstream of receptors other than the TCR, such as integrins and chemokine receptors...
  2. doi Activation of the small GTPase Rac2 via the B cell receptor regulates B cell adhesion and immunological-synapse formation
    Eloisa Arana
    Lymphocyte Interaction Laboratory, Cancer Research UK, London Research Institute, Lincoln s Inn Fields Laboratories, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Immunity 28:88-99. 2008
    ..We postulate that this critical role for Rac2 in mediating B cell adhesion and IS formation might apply in all lymphocytes...
  3. pmc Down syndrome: searching for the genetic culprits
    Eva Lana-Elola
    MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK
    Dis Model Mech 4:586-95. 2011
    ....
  4. pmc Vav1 transduces T cell receptor signals to the activation of phospholipase C-gamma1 via phosphoinositide 3-kinase-dependent and -independent pathways
    Lucinda F Reynolds
    National Institute for Medical Research, London NW7 1AA, United Kingdom
    J Exp Med 195:1103-14. 2002
    ..We show that this latter function is independent of PI3K...
  5. pmc Crucial structural role for the PH and C1 domains of the Vav1 exchange factor
    Jonathan Rapley
    Division of Molecular Structure, and National Institute for Medical Research, The Ridgeway, London NW7 1AA, UK
    EMBO Rep 9:655-61. 2008
    ..In contrast to previous reports, this structure shows that there are no direct contacts between the GTPase and C1 domain but instead suggests new mechanisms for the regulation of Vav1 activity...
  6. pmc Mechanism and function of Vav1 localisation in TCR signalling
    Olga Ksionda
    Division of Immune Cell Biology, MRC National Institute for Medical Research, London NW7 1AA, UK
    J Cell Sci 125:5302-14. 2012
    ..We propose that Vav1 is recruited to the IS by binding to SLP76 and that this interaction is critical for the transduction of signals leading to calcium flux...
  7. pmc A novel Rac-dependent checkpoint in B cell development controls entry into the splenic white pulp and cell survival
    Robert B Henderson
    Division of Immune Cell Biology, Medical Research Council National Institute for Medical Research, London NW7 1AA, England, UK
    J Exp Med 207:837-53. 2010
    ..Thus, these studies identify a novel developmental checkpoint that coincides with B cell positive selection...
  8. pmc An additional human chromosome 21 causes suppression of neural fate of pluripotent mouse embryonic stem cells in a teratoma model
    Afua Mensah
    Centre for Haematology, Institute of Cell and Molecular Science, Barts and The London, Queen Mary s School of Medicine, University of London, 4 Newark Street, London E1 2AT, UK
    BMC Dev Biol 7:131. 2007
    ..The exact molecular cause of this reduction, and the role played by increased dosage of individual HSA21 genes, remain unknown...
  9. ncbi Commentary: New insights into the complexity of phosphatidylinositol lipid signaling in B lymphocytes
    Victor L J Tybulewicz
    Division of Immune Cell Biology, National Institute for Medical Research, London, UK
    Eur J Immunol 34:2964-7. 2004
    ..These results highlight the need for careful measurement of PI3K activity in gene-targeted mice and cells, by directly measuring levels of the 3-PI lipids...
  10. ncbi New techniques to understand chromosome dosage: mouse models of aneuploidy
    Victor L J Tybulewicz
    Division of Immune Cell Biology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
    Hum Mol Genet 15:R103-9. 2006
    ....
  11. ncbi Rho family GTPases and their regulators in lymphocytes
    Victor L J Tybulewicz
    Division of Immune Cell Biology, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
    Nat Rev Immunol 9:630-44. 2009
    ....
  12. ncbi Vav1: a key signal transducer downstream of the TCR
    Victor L J Tybulewicz
    Division of Immune Cell Biology, National Institute for Medical Research, London, UK
    Immunol Rev 192:42-52. 2003
    ..In particular, Vav1 is required for efficient TCR-induced conjugate formation with antigen presenting cells (APCs), activation of the integrin leukocyte function-associated antigen-1 (LFA-1) and cell polarization...
  13. pmc Chemokines and the immunological synapse
    Victor L J Tybulewicz
    National Institute for Medical Research, The Ridgeway, Mill Hill, London, UK
    Immunology 106:287-8. 2002
  14. doi Redundant role for Zap70 in B cell development and activation
    Farnaz Fallah-Arani
    Division of Immune Cell Biology, MRC National Institute for Medical Research, London, UK
    Eur J Immunol 38:1721-33. 2008
    ..However, we show that Zap70 can rescue the defective positive selection of immature B cells into the recirculating pool in Syk-deficient mice, demonstrating functional redundancy between these two kinases...
  15. ncbi Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling
    Marita J Walmsley
    Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK
    Science 302:459-62. 2003
    ..Both GTPases were required to transduce BCR signals leading to proliferation, survival and up-regulation of BAFF-R, a receptor for BAFF, a key survival molecule required for B cell development and maintenance...
  16. pmc Rac GTPases play critical roles in early T-cell development
    Celine Dumont
    Division of Immune Cell Biology, Medical Research Council MRC National Institute for Medical Research, London, UK
    Blood 113:3990-8. 2009
    ..These results show that a pathway containing Vav and Rac proteins may negatively regulate Notch signaling during early thymic development...
  17. ncbi Lineage-specific requirement for the PH domain of Vav1 in the activation of CD4+ but not CD8+ T cells
    Antonella Prisco
    Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
    Immunity 23:263-74. 2005
    ..Unexpectedly, the mutation selectively affects TCR-induced proliferation of CD4(+) but not CD8(+) T cells, demonstrating differences in the wiring of TCR signaling pathways between the two lineages...
  18. ncbi Vav1 transduces T cell receptor signals to the activation of the Ras/ERK pathway via LAT, Sos, and RasGRP1
    Lucinda F Reynolds
    Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom
    J Biol Chem 279:18239-46. 2004
    ..We propose that reduced LAT phosphorylation is the key reason for defective TCR-induced calcium flux and ERK activation in Vav1-deficient cells...
  19. pmc Critical roles for Rac GTPases in T-cell migration to and within lymph nodes
    Mustapha Faroudi
    Medical Research Council National Institute for Medical Research, London, UK
    Blood 116:5536-47. 2010
    ..These multiple defects stem from critical roles for Rac1 and Rac2 in transducing chemokine and sphingosine-1-phosphate receptor 1 signals leading to motility and adhesion...
  20. pmc The BAFF receptor transduces survival signals by co-opting the B cell receptor signaling pathway
    Edina Schweighoffer
    Division of Immune Cell Biology, MRC National Institute for Medical Research, London NW7 1AA, UK
    Immunity 38:475-88. 2013
    ....
  21. ncbi Distinct roles for the linker region tyrosines of Syk in FcepsilonRI signaling in primary mast cells
    Maria Simon
    Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom
    J Biol Chem 280:4510-7. 2005
    ..Finally we show that Tyr317 functions as a negative regulatory site and that its mutation can partially compensate for the loss of both Tyr342 and Tyr346...
  22. pmc Altered regulation of tau phosphorylation in a mouse model of down syndrome aging
    Olivia Sheppard
    University College London Institute of Neurology, London, UK
    Neurobiol Aging 33:828.e31-44. 2012
    ..It is possible that a similar mechanism may also occur in people with DS...
  23. pmc Function of the nucleotide exchange activity of vav1 in T cell development and activation
    Alexander Saveliev
    1Division of Immune Cell Biology, MRC National Institute for Medical Research, London NW7 1AA, UK
    Sci Signal 2:ra83. 2009
    ..Thus, in T cells, the GEF activity of Vav1 is essential for some, but not all, of its functions...
  24. doi Characterization of the roles of Rac1 and Rac2 GTPases in lymphocyte development
    Celine Dumont
    Division of Immune Cell Biology, National Institute for Medical Research, London, United Kingdom
    Methods Enzymol 439:235-54. 2008
    ..Analysis of these processes in mice deficient in these GTPases can illuminate their roles in transducing signals from these different receptors...
  25. pmc Alterations to dendritic spine morphology, but not dendrite patterning, of cortical projection neurons in Tc1 and Ts1Rhr mouse models of Down syndrome
    Matilda A Haas
    Division of Molecular Neurobiology, Medical Research Council National Institute for Medical Research, London, United Kingdom
    PLoS ONE 8:e78561. 2013
    ..This data suggests that dendritic spine abnormalities may be a more important contributor to cognitive deficits in DS models, rather than overall neuronal architecture defects...
  26. pmc Generation of a panel of antibodies against proteins encoded on human chromosome 21
    Frances K Wiseman
    Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK
    J Negat Results Biomed 9:7. 2010
    ..To this end, we have generated a panel of antibodies raised against proteins encoded by genes on human chromosome 21 that are known to be expressed in the adult brain of Tc1 mice..
  27. pmc Preservation of long-term memory and synaptic plasticity despite short-term impairments in the Tc1 mouse model of Down syndrome
    Elise Morice
    Division of Neurophysiology, National Institute for Medical Research, London NW7 1AA, United Kingdom
    Learn Mem 15:492-500. 2008
    ..Our observations also provide further evidence that STM and LTM for hippocampus-dependent tasks are subserved by parallel processing streams...
  28. pmc Perturbed hematopoiesis in the Tc1 mouse model of Down syndrome
    Kate A Alford
    Division of Immune Cell Biology, Medical Research Council National Institute for Medical Research, London, UK
    Blood 115:2928-37. 2010
    ....
  29. ncbi Vav1 transduces TCR signals required for LFA-1 function and cell polarization at the immunological synapse
    Laurence Ardouin
    National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, Great Britain
    Eur J Immunol 33:790-7. 2003
    ..These data demonstrate that Vav1 transduces signals to only a subset of cytoskeleton-dependent events at the immunological synapse...
  30. ncbi Unexpected requirement for ZAP-70 in pre-B cell development and allelic exclusion
    Edina Schweighoffer
    National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom
    Immunity 18:523-33. 2003
    ..Whereas mice deficient in Syk show a partial block at this step, mice mutant in both Syk and ZAP-70 show a complete block at the pro-B cell stage and a failure of heavy chain allelic exclusion, hallmarks of defective pre-BCR signaling...
  31. pmc Overexpression of the Hspa13 (Stch) gene reduces prion disease incubation time in mice
    Julia Grizenkova
    Medical Research Council MRC Prion Unit, University College London UCL Institute of Neurology, London, United Kingdom
    Proc Natl Acad Sci U S A 109:13722-7. 2012
    ..These data further implicate Hsp70-like molecular chaperones in protein misfolding disorders such as prion disease...
  32. doi Lymphocyte signaling: beyond knockouts
    Alexander Saveliev
    Medical Research Council National Institute for Medical Research, London, UK
    Nat Immunol 10:361-4. 2009
    ..In these cases, gene targeting to 'knock in' subtle point mutations might provide more accurate insight into protein function. However, to be informative, such mutations must be carefully based on structural and biophysical data...
  33. pmc Structural correlates of active-staining following magnetic resonance microscopy in the mouse brain
    Jon O Cleary
    Centre for Advanced Biomedical Imaging, Department of Medicine and Institute of Child Health, University College London, London, UK
    Neuroimage 56:974-83. 2011
    ....
  34. pmc Down syndrome and the molecular pathogenesis resulting from trisomy of human chromosome 21
    Aarti Ruparelia
    Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK
    J Biomed Res 24:87-99. 2010
    ..This is opening the way for exciting new studies of potential therapeutics for aspects of Down syndrome, particularly the learning and memory deficits...
  35. pmc Down syndrome--recent progress and future prospects
    Frances K Wiseman
    Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London, UK
    Hum Mol Genet 18:R75-83. 2009
    ..In particular, the use of chromosome engineering to generate new trisomic mouse models and large-scale studies of genotype-phenotype relationships in patients are likely to significantly contribute to the future understanding of DS...
  36. pmc IKK-induced NF-κB1 p105 proteolysis is critical for B cell antibody responses to T cell-dependent antigen
    Emilie Jacque
    Division of Immune Cell Biology, MRC National Institute for Medical Research, London NW7 1AA, England, UK
    J Exp Med 211:2085-101. 2014
    ..Our study identifies critical B cell-intrinsic functions for IKK-induced NF-κB1 p105 proteolysis in the antigen-induced survival and differentiation of FM B cells, which are essential for T-dependent antibody responses...
  37. pmc Themis2 is not required for B cell development, activation, and antibody responses
    Harald Hartweger
    Medical Research Council, National Institute for Medical Research, London NW7 1AA, United Kingdom and
    J Immunol 193:700-7. 2014
    ..Surprisingly, we found that Themis2 is not required for B cell development, for activation, or for Ab responses either to model Ags or to influenza viral infection. ..
  38. ncbi Requirement of Rac1 and Rac2 expression by mature dendritic cells for T cell priming
    Federica Benvenuti
    Unité INSERM 365, Institut Curie, 26 Rue d Ulm, 75005 Paris, France
    Science 305:1150-3. 2004
    ..The Rho family guanosine triphosphatases Rac1 and Rac2 but not Rho itself control the formation of dendrites in mature DCs, their polarized short-range migration toward T cells, and T cell priming...
  39. ncbi ERM proteins regulate cytoskeleton relaxation promoting T cell-APC conjugation
    Sophie Faure
    Institut Cochin, Departement de Biologie Cellulaire, Institut National de la Santé et de la Recherche Médicale U567 Centre National de la Recherche Scientifique UMR 8104, Universite Rene Descartes, 22 rue Mechain, 75014 Paris, France
    Nat Immunol 5:272-9. 2004
    ..These findings identify an antigen-dependent molecular pathway that favors immunological synapse formation and the subsequent development of an effective immune response...
  40. ncbi Vav1, but not Vav2, contributes to platelet aggregation by CRP and thrombin, but neither is required for regulation of phospholipase C
    Andrew C Pearce
    Department of Pharmacology, University of Oxford, United Kingdom
    Blood 100:3561-9. 2002
    ..The present study has provided evidence for a possible role of Vav1 but not Vav2 in the later stages of platelet aggregation...
  41. pmc An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes
    Aideen O'Doherty
    Department of Neurodegenerative Disease, Institute of Neurology, Queen Square, London WC1N 3BG, UK
    Science 309:2033-7. 2005
    ..Transchromosomic mouse lines such as Tc1 may represent useful genetic tools for dissecting other human aneuploidies...
  42. ncbi Cutting edge: Rac GTPases sensitize activated T cells to die via Fas
    Madhu Ramaswamy
    Immunoregulation Unit, Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 179:6384-8. 2007
    ..Activating Rac signaling may be a novel way to sensitize chronically stimulated lymphocytes to Fas-induced apoptosis, an important goal in the treatment of autoimmune diseases...
  43. ncbi CD19 is essential for B cell activation by promoting B cell receptor-antigen microcluster formation in response to membrane-bound ligand
    David Depoil
    Lymphocyte Interaction Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln s Inn Fields, London WC2A 3PX, UK
    Nat Immunol 9:63-72. 2008
    ....
  44. pmc Syk-mediated translocation of PI3Kdelta to the leading edge controls lamellipodium formation and migration of leukocytes
    Jurgen Schymeinsky
    Department of Physiology, Ludwig Maximilians University Munich, Munich, Germany
    PLoS ONE 2:e1132. 2007
    ..These data imply a novel role of Syk via PI3K p110delta signaling for beta2 integrin-mediated migration which is a prerequisite for efficient PMN recruitment in vivo...
  45. pmc GPVI potentiation of platelet activation by thrombin and adhesion molecules independent of Src kinases and Syk
    Sascha C Hughan
    Centre for Cardiovascular Sciences, Institute of Biomedical Research, University of Birmingham, UK
    Arterioscler Thromb Vasc Biol 27:422-9. 2007
    ..The present study investigates the role of Src and Syk tyrosine kinases in signaling by G-protein coupled and platelet adhesion receptors...
  46. ncbi A critical role for Syk protein tyrosine kinase in Fc receptor-mediated antigen presentation and induction of dendritic cell maturation
    Christine Sedlik
    Institut National de la Santé et de la Recherche Médicale Unité 520, Institut Curie, Paris, France
    J Immunol 170:846-52. 2003
    ..Therefore, protein tyrosine phosphorylation by Syk represents a novel pathway for the induction of DC maturation...
  47. ncbi NKG2D triggers cytotoxicity in mouse NK cells lacking DAP12 or Syk family kinases
    Simona Zompi
    Department of Immunology, Pasteur Institute, 25 28 rue Dr Roux, 75015 Paris, France
    Nat Immunol 4:565-72. 2003
    ....
  48. ncbi Natural cytotoxicity uncoupled from the Syk and ZAP-70 intracellular kinases
    Francesco Colucci
    Laboratory for Cytokines and Lymphoid Development, The Pasteur Institute, Paris, France
    Nat Immunol 3:288-94. 2002
    ..This suggests that distinct and redundant signaling pathways act synergistically to trigger natural cytotoxicity...
  49. pmc DYRK1A-dosage imbalance perturbs NRSF/REST levels, deregulating pluripotency and embryonic stem cell fate in Down syndrome
    Claudia Canzonetta
    Institute of Cell and Molecular Science, Barts and The London, Queen Mary s School of Medicine and Dentistry, University of London, 4 Newark Street, London E1 2AT, UK
    Am J Hum Genet 83:388-400. 2008
    ....
  50. ncbi The tyrosine kinase Syk is required for light chain isotype exclusion but dispensable for the negative selection of B cells
    Josephine Meade
    Laboratory of Lymphocyte Signaling and Development, Molecular Immunology Programme, The Babraham Institute, Cambridge, GB
    Eur J Immunol 34:1102-10. 2004
    ..Thus signaling events that mediate negative selection can still occur in the absence of Syk. This may be due to redundancy with zeta-associated protein 70 (ZAP-70), which we demonstrate to be expressed in immature B cells...
  51. pmc Species-specific transcription in mice carrying human chromosome 21
    Michael D Wilson
    Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK
    Science 322:434-8. 2008
    ....
  52. ncbi A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2
    Katsue Suzuki-Inoue
    Department of Clinical and Laboratory Medicine, University of Yamanashi, Shimokato Tamaho Nakakoma, Yamanashi 409 3898, Japan
    Blood 107:542-9. 2006
    ..CLEC-2 is the first C-type lectin receptor to be found on platelets which signals through this novel pathway...
  53. ncbi Requirement for Rac1 in a K-ras induced lung cancer in the mouse
    Joseph L Kissil
    Program in Molecular Oncogenesis, The Wistar Institute, Philadelphia, PA 19104, USA
    Cancer Res 67:8089-94. 2007
    ..These data show a specific requirement for Rac1 function in cells expressing oncogenic K-ras...
  54. ncbi Functional analysis of activating receptor LMIR4 as a counterpart of inhibitory receptor LMIR3
    Kumi Izawa
    Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4 6 1 Shirokanedai, Minato ku, Tokyo 108 8639, Japan
    J Biol Chem 282:17997-8008. 2007
    ..Collectively, these results suggest that the innate immune system is at least in part regulated by the qualitative and quantitative balance of the paired receptors LMIR3 and LMIR4...
  55. pmc Beta1 integrin activates Rac1 in Schwann cells to generate radial lamellae during axonal sorting and myelination
    Alessandro Nodari
    Department of Biological and Technological Research, San Raffaele Scientific Institute, 20132 Milan, Italy
    J Cell Biol 177:1063-75. 2007
    ..Thus, increased activation of Rac1 by beta1 integrins allows Schwann cells to switch from migration/elongation to the extension of radial membranes required for axonal sorting and myelination...