Research Topics
Genomes and Genes | Bart VanhaesebroeckSummaryAffiliation: University College London Country: UK Publications
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Publications
Distinct PI(3)Ks mediate mitogenic signalling and cell migration in macrophagesB Vanhaesebroeck
Ludwig Institute for Cancer Research, University College London Branch, UK
Nat Cell Biol 1:69-71. 1999
Antigen receptor signalling: a distinctive role for the p110delta isoform of PI3KKlaus Okkenhaug
Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, UK, CB2 4AT
Trends Immunol 28:80-7. 2007..The p110delta isoform of PI3K is the main source of PI3K activity following antigen recognition by B cells, T cells and mast cells. Here, we review the roles of p110delta in regulating antigen-dependent responses in these cell types...- Autophosphorylation of p110delta phosphoinositide 3-kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivoB Vanhaesebroeck
Ludwig Institute for Cancer Research, 91 Riding House Street, London W1P 8BT, UK
EMBO J 18:1292-302. 1999..In summary, we show that PI3Ks are subject to regulatory phosphorylations in vivo similar to those identified under in vitro conditions, identifying a new level of control of these signalling molecules... - Signaling by distinct classes of phosphoinositide 3-kinasesB Vanhaesebroeck
Ludwig Institute for Cancer Research, 91 Riding House Street, London, W1P 8BT, United Kingdom
Exp Cell Res 253:239-54. 1999..Here we review the activation mechanisms of the different types of PI3Ks and their downstream actions, with focus on the PI3Ks that are acutely triggered by extracellular stimulation... - The PI3K-PDK1 connection: more than just a road to PKBB Vanhaesebroeck
Cell Signalling Group, Ludwig Institute for Cancer Research, 91 Riding House Street, London W1P 8BT, U K
Biochem J 346:561-76. 2000.... - Synthesis and function of 3-phosphorylated inositol lipidsB Vanhaesebroeck
Ludwig Institute for Cancer Research, Riding House Street, London W1W 7BS
Annu Rev Biochem 70:535-602. 2001..This field is now moving toward a genetic dissection of 3-phosphoinositide action in a variety of model organisms. Such approaches will reveal the true role of the 3-phosphoinositides at the organismal level in health and disease... - Signalling by PI3K isoforms: insights from gene-targeted miceBart Vanhaesebroeck
Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK
Trends Biochem Sci 30:194-204. 2005..Targeting strategies that take into account the complex interplay between members of the PI3K family will be crucial to gain a full understanding of the physiological roles of the isoforms of PI3K... - Isoform-specific functions of phosphoinositide 3-kinases: p110 delta but not p110 gamma promotes optimal allergic responses in vivoKhaled Ali
Centre for Cell Signalling, Institute of Cancer, Queen Mary University of London, Sir John Vane Research Centre, Charterhouse Square, London, United Kingdom
J Immunol 180:2538-44. 2008..These observations identify p110delta as a key therapeutic target among PI3K isoforms for allergy- and mast cell-related diseases... 
Control of axonal growth and regeneration of sensory neurons by the p110delta PI 3-kinaseBritta J Eickholt
Medical Research Council Centre for Developmental Neurobiology, King s College London, London, United Kingdom
PLoS ONE 2:e869. 2007..Our data identify p110delta as an important signaling component for efficient axonal elongation in the developing and regenerating nervous system...- Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulationLazaros C Foukas
Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK
Nature 441:366-70. 2006..These findings demonstrate a critical role for p110alpha in growth factor and metabolic signalling and also suggest an explanation for selective mutation or overexpression of p110alpha in a variety of cancers... - Key role of the p110delta isoform of PI3K in B-cell antigen and IL-4 receptor signaling: comparative analysis of genetic and pharmacologic interference with p110delta function in B cellsAntonio Bilancio
Ludwig Institute for Cancer Research, 91 Riding House Street, London, W1W 7BS, United Kingdom
Blood 107:642-50. 2006.... - Class I phosphoinositide 3-kinase p110beta is required for apoptotic cell and Fcgamma receptor-mediated phagocytosis by macrophagesYann Leverrier
Ludwig Institute for Cancer Research, Royal Free and University College Medical School Branch, 91 Riding House Street, London W1W 7BS, United Kingdom
J Biol Chem 278:38437-42. 2003..Our findings demonstrate that p110beta is the major class I catalytic isoform required for apoptotic cell and Fcgamma receptor-mediated phagocytosis by primary macrophages... - Essential role for the p110delta phosphoinositide 3-kinase in the allergic responseKhaled Ali
Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK
Nature 431:1007-11. 2004..Inactivation of p110delta protects mice against anaphylactic allergic responses. These results identify p110delta as a new target for therapeutic intervention in allergy and mast-cell-related pathologies... - The p110delta isoform of PI 3-kinase negatively controls RhoA and PTENEvangelia A Papakonstanti
Ludwig Institute for Cancer Research, London, UK
EMBO J 26:3050-61. 2007..This work identifies the RhoA/ROCK pathway as a major target of p110delta-mediated PI3K signalling, and establishes for the first time that PI3K controls itself, via a feedback loop involving PTEN... - Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant miceKlaus Okkenhaug
Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK
Science 297:1031-4. 2002..They also developed inflammatory bowel disease. These results reveal a selective role for p110delta in immunity... - Class IA phosphoinositide 3-kinases are obligate p85-p110 heterodimersBarbara Geering
Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, United Kingdom
Proc Natl Acad Sci U S A 104:7809-14. 2007..These results argue against a role of free p85 in PI3K signaling and provide insights into the nonredundant functions of the different class IA PI3K isoforms... - Regulation of p110delta PI 3-kinase gene expressionKlaartje Kok
Centre for Cell Signalling, Institute of Cancer, Queen Mary University of London, Charterhouse Square, London, United Kingdom
PLoS ONE 4:e5145. 2009..This also applies to the leukocyte-enriched p110delta catalytic subunit of PI3K, an enzyme that has attracted widespread interest because of its role in immunity and allergy... - Quantification of gel-separated proteins and their phosphorylation sites by LC-MS using unlabeled internal standards: analysis of phosphoprotein dynamics in a B cell lymphoma cell linePedro R Cutillas
Cell Signalling Group, Ludwig Institute for Cancer Research, 91 Riding House Street, London, W1W 7BS
Mol Cell Proteomics 4:1038-51. 2005..Our results illustrate the capacity of this conceptually simple LC-MS method for quantification of gel-separated proteins and their phosphorylation sites and for quantitative profiling of biological systems... - Ultrasensitive and absolute quantification of the phosphoinositide 3-kinase/Akt signal transduction pathway by mass spectrometryPedro R Cutillas
Cell Signaling in Cancer Laboratory, Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, United Kingdom
Proc Natl Acad Sci U S A 103:8959-64. 2006..Due to its special analytical capabilities and potential for multiplexing, this approach could contribute significantly to cell-signaling studies and to the development and implementation of personalized cancer therapies... 
Inhibition of class I phosphoinositide 3-kinase activity impairs proliferation and triggers apoptosis in acute promyelocytic leukemia without affecting atra-induced differentiationClotilde Billottet
Centre for Cell Signalling, Queen Mary University of London, Institute of Cancer, Barts and the London School of Medicine, John Vane Science Centre University College London, London, United Kingdom
Cancer Res 69:1027-36. 2009..Addition of PI3K inhibitors to induction treatment regimens may provide therapeutic benefit...- The p110δ isoform of the kinase PI(3)K controls the subcellular compartmentalization of TLR4 signaling and protects from endotoxic shockEzra Aksoy
Centre for Cell Signaling, Barts Institute of Cancer, Queen Mary, University of London, London, UK
Nat Immunol 13:1045-54. 2012..In line with that altered signaling output, p110δ-deficient mice showed enhanced endotoxin-induced death. Thus, by controlling the 'topology' of TLR4 signaling complexes, p110δ balances overall homeostasis in the TLR4 pathway... - The emerging mechanisms of isoform-specific PI3K signallingBart Vanhaesebroeck
Centre for Cell Signalling, Institute of Cancer, Queen Mary University of London, Charterhouse Square, London, UK
Nat Rev Mol Cell Biol 11:329-41. 2010..A better understanding of how the different PI3K isoforms are regulated and control signalling could uncover their roles in pathology and reveal in which disease contexts their blockade could be most beneficial... - Activity of any class IA PI3K isoform can sustain cell proliferation and survivalLazaros C Foukas
Centre for Cell Signalling, Institute of Cancer, Queen Mary University of London, London EC1M 6BQ, United Kingdom
Proc Natl Acad Sci U S A 107:11381-6. 2010..Such functional redundancy of class IA PI3K isoforms upon sustained PI3K inhibition has implications for the development and use of PI3K inhibitors in cancer... - Quantitative profile of five murine core proteomes using label-free functional proteomicsPedro R Cutillas
Cell Signalling Group, Ludwig Institute for Cancer Research, London, UK
Mol Cell Proteomics 6:1560-73. 2007.... - Gene targeting: attention to detailBart Vanhaesebroeck
Ludwig Institute for Cancer Research, London, United Kingdom
Cell 118:274-6. 2004..When it comes to silencing genes in mice, not all approaches are equal. An example published in this issue of Cell (Patrucco et al., 2004) suggests that caution should be used when validating potential drug targets by genetic disruption... - A new tool to dissect the function of p70 S6 kinaseBenoit Bilanges
Centre for Cell Signalling, Institute of Cancer, Queen Mary University of London, Charterhouse Square, London, UK
Biochem J 431:e1-3. 2010..S6K1 inhibitors may ultimately be useful in the treatment of diseases such as cancer where S6K1 is overexpressed, but most importantly in metabolic disease such as insulin resistance and obesity... - Regulation of breast cancer cell chemotaxis by the phosphoinositide 3-kinase p110deltaCarol Sawyer
Cell Signalling Group, The Ludwig Institute for Cancer Research, University College and Royal Free Medical School Branch, London, W1W 7BS
Cancer Res 63:1667-75. 2003..The potential clinical implications of p110delta expression in non-WBC-derived tumors are discussed... - PI3K: from the bench to the clinic and backBart Vanhaesebroeck
University of London, London, EC1M 6BQ, UK
Curr Top Microbiol Immunol 347:1-19. 2010..PI3K will most likely be no exception. Below, we describe some of these early "surprises" and how these inform and shape basic science investigations... - Oncogenic transformation induced by the p110beta, -gamma, and -delta isoforms of class I phosphoinositide 3-kinaseSohye Kang
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, BCC 239, La Jolla, CA 92037, USA
Proc Natl Acad Sci U S A 103:1289-94. 2006.... - PI3K in lymphocyte development, differentiation and activationKlaus Okkenhaug
Molecular Immunology Programme, The Babraham Institute, Cambridge CB2 4AT, UK
Nat Rev Immunol 3:317-30. 2003..Additional recent work has provided new insights into the molecular interactions that lead to PI3K activation and the signalling pathways that are regulated by PI3K... - Glucose-potentiated chemotaxis in human vascular smooth muscle is dependent on cross-talk between the PI3K and MAPK signaling pathwaysMalcolm Campbell
Department of Clinical Biochemistry and Metabolic Medicine, Queen s University Belfast, Institute of Clinical Science, Royal Victoria Hospital, Grosvenor Road, Belfast, UK
Circ Res 95:380-8. 2004..In conclusion, glucose sensitizes VSMC to serum, inducing chemotaxis via pathways involving p110beta-PI3K, Akt, mTOR, and ERK1/2 MAPK. Cross-talk between the PI3K and MAPK pathways is necessary for VSMC chemotaxis under these conditions... - The p110 delta of PI3K plays a critical role in NK cell terminal maturation and cytokine/chemokine generationHailong Guo
Laboratory of Molecular Immunology, Blood Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA
J Exp Med 205:2419-35. 2008..These results reveal a previously unrecognized role of PI3K-p110 delta in NK cell development and effector functions... - Activation of phosphoinositide 3-kinase by the NBS1 DNA repair protein through a novel activation motifYen Chung Chen
Institute of Biochemistry and Molecular Biology, National Yang Ming University, No 155, Li Nong St, Sec 2, Peitou, Taipei 112, Taiwan
J Mol Med (Berl) 86:401-12. 2008..These results demonstrate that NBS1 can function as an adaptor/activator of p110alpha PI 3-kinase through a novel activation motif, consistent with its possible role in cell transformation and tumorigenesis... - Two distinct phosphoinositide 3-kinases mediate polypeptide growth factor-stimulated PKB activationAlexandre Arcaro
Lung Cancer Biology Group, Division of Medicine, Imperial College Faculty of Medicine, Du Cane Road, London W12 0NN, UK
EMBO J 21:5097-108. 2002..A dominant-negative PI3KC2beta blocked both PKB activation and SCLC cell growth in response to SCF. Together our data provide novel insights into the specificity and functional significance of PI3K signalling in human cancer... - Stat3-induced apoptosis requires a molecular switch in PI(3)K subunit compositionKathrine Abell
Mammary Apoptosis and Development Group, Department of Pathology, Tennis Court Road, University of Cambridge, Cambridge CB2 1QP, UK
Nat Cell Biol 7:392-8. 2005..We propose a novel mechanism in which Stat3 regulates apoptosis by inducing expression of distinct PI(3)K regulatory subunits to downregulate PI(3)K-Akt-mediated survival signalling... - Essential role for the p110delta isoform in phosphoinositide 3-kinase activation and cell proliferation in acute myeloid leukemiaPierre Sujobert
Service d Hematologie, Hopital Cochin, AP HP, 27 rue du Faubourg Saint Jacques, 75014, Paris, France
Blood 106:1063-6. 2005..Moreover, IC87114 inhibited AML cell proliferation without affecting the proliferation of normal hematopoietic progenitor cells. These observations identify p110delta as a potential therapeutic target in AML... - Sequential activation of class IB and class IA PI3K is important for the primed respiratory burst of human but not murine neutrophilsAlison M Condliffe
The Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, UK
Blood 106:1432-40. 2005..These results start to define which PI3K isoforms are responsible for modulating neutrophil responsiveness to infection and inflammation... - The p110delta isoform of phosphoinositide 3-kinase controls clonal expansion and differentiation of Th cellsKlaus Okkenhaug
Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
J Immunol 177:5122-8. 2006..Thus, p110delta contributes significantly to Th cell expansion and differentiation in vitro and in vivo, also in the context of CD28 costimulation... - Cell target genes of Epstein-Barr virus transcription factor EBNA-2: induction of the p55alpha regulatory subunit of PI3-kinase and its role in survival of EREB2.5 cellsLindsay C Spender
Department of Virology, Imperial College Faculty of Medicine, Norfolk Place, London W2 1PG, UK
J Gen Virol 87:2859-67. 2006..p55alpha is thus a functional target of EBNA2 in EREB2.5 cells and the specific regulation of p55alpha by EBV will provide an opportunity to investigate the physiological function of p55alpha in this human cell line... - Cutting edge: the phosphoinositide 3-kinase p110 delta is critical for the function of CD4+CD25+Foxp3+ regulatory T cellsDaniel T Patton
Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
J Immunol 177:6598-602. 2006..The identification of p110delta as an intracellular signaling protein that regulates the activity of CD4+CD25+Foxp3+ Tregs may facilitate the further elucidation of the molecular mechanisms responsible for Treg-mediated suppression... - The Pten/PI3K pathway governs the homeostasis of Valpha14iNKT cellsHiroyuki Kishimoto
Department of Molecular Biology, Akita University School of Medicine, Hondo 1 1 1, Akita 0108 543, Japan
Blood 109:3316-24. 2007..Thus, the Pten/PI3K pathway is indispensable for the homeostasis and antitumor surveillance function of Valpha14iNKT cells... - Human platelets contain p110delta phosphoinositide 3-kinaseJin Zhang
Kimmel Cancer Center and Cardeza Foundation for Hematological Research, Thomas Jefferson University, JAH 476, 1020 Locust Street, Philadelphia, PA 19107, USA
Biochem Biophys Res Commun 296:178-81. 2002..We report that p110delta is present in association with p85alpha and p85beta in platelets, both in cytosolic and cytoskeletal fractions. The latter finding is consistent with the proposed role of p110delta in cytoskeletal function... - Charging the batteries to heal wounds through PI3KBart Vanhaesebroeck
Nat Chem Biol 2:453-5. 2006 - Role of the p110delta PI 3-kinase in integrin and ITAM receptor signalling in plateletsYotis A Senis
Centre for Cardiovascular Sciences, Division of Medical Sciences, Institute of Biomedical Research, Wolfson Drive, The Medical School, University of Birmingham, Edgbaston, Birmingham, UK
Platelets 16:191-202. 2005..The more pronounced inhibitory effect of LY294002 and wortmannin indicates that other isoforms of PI 3-kinase play a more significant role in signalling by the two platelet glycoprotein receptors... - The p110beta isoform of phosphoinositide 3-kinase signals downstream of G protein-coupled receptors and is functionally redundant with p110gammaJulie Guillermet-Guibert
Center for Cell Signaling, Institute of Cancer, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, United Kingdom
Proc Natl Acad Sci U S A 105:8292-7. 2008..p110beta, which shows a much broader tissue distribution than the leukocyte-restricted p110gamma, could thus provide a conduit for GPCR-linked PI3K signaling in the many cell types where p110gamma expression is low or absent... - Activation of c-Kit in dendritic cells regulates T helper cell differentiation and allergic asthmaNandini Krishnamoorthy
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, 3459 Fifth Avenue, Pittsburgh, Pennsylvania 15213, USA
Nat Med 14:565-73. 2008..Collectively, these results highlight the importance of the c-Kit-PI3 kinase-IL-6 signaling axis in DCs in regulating T cell responses... - Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migrationMariona Graupera
Centre for Cell Signalling, Institute of Cancer, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK
Nature 453:662-6. 2008..These results provide the first in vivo evidence for p110-isoform selectivity in endothelial PI3K signalling during angiogenesis... - Role of the phosphoinositide 3-kinase p110delta in generation of type 2 cytokine responses and allergic airway inflammationBaher F Nashed
CIHR National Training Program in Allergy and Asthma Research and Department of Immunology, University of Manitoba, Winnipeg, Canada
Eur J Immunol 37:416-24. 2007..These data demonstrate a novel functional role for p110delta signaling in induction of type 2 responses in vivo and may offer a new therapeutic target for Th2-mediated airway disease... - Requirement for phosphoinositide 3-kinase p110delta signaling in B cell antigen receptor-mediated antigen presentationMonther M Al-Alwan
Department of Immunology, University of Manitoba, Winnipeg, Canada
J Immunol 178:2328-35. 2007..Our data demonstrate a role for p110delta signaling in B cell Ag presentation function, implicating 3-phosphoinositides and their targets in the latter stages of this process... - Airway inflammation: chemokine-induced neutrophilia and the class I phosphoinositide 3-kinasesMatthew J Thomas
Novartis Institutes for BioMedical Research, Horsham, UK
Eur J Immunol 35:1283-91. 2005..These data resolve the complexities of chemokine-induced neutrophilia and PI3K signaling and define the gamma isoform as a promising target for new therapeutics to treat airway inflammatory diseases... - Inactivation of PI3Kgamma and PI3Kdelta distorts T-cell development and causes multiple organ inflammationHong Ji
Merck Serono S A, Geneva Research Center, Geneva, Switzerland
Blood 110:2940-7. 2007..Thus, the pathology in the p110gammadelta-deficient mice is likely to be secondary to a developmental block in the thymus that leads to lymphopenia-associated inflammatory responses... - Cutting edge: differential roles for phosphoinositide 3-kinases, p110gamma and p110delta, in lymphocyte chemotaxis and homingKarin Reif
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA
J Immunol 173:2236-40. 2004..These observations establish that p110gamma and p110delta function in lymphocyte chemotaxis, and show differential roles for PI3K family members in B and T cell migration...