Pik3cd

Summary

Gene Symbol: Pik3cd
Description: phosphatidylinositol 3-kinase catalytic delta polypeptide
Alias: 2410099E07Rik, 2610208K16Rik, AW545373, p110delta, PI3-kinase subunit delta, PI3K-delta, PI3Kdelta, catalytic phosphatidylinositol 3-kinase delta, p100 delta, phosphatidylinositol 3-kinase catalytic subunit delta, phosphatidylinositol 3-kinase p110 delta, phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform, phosphatidylinositol-4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta isoform, phosphoinositide 3 kinase P110delta, ptdIns-3-kinase subunit delta, ptdIns-3-kinase subunit p110-delta
Species: mouse

Top Publications

  1. pmc A crucial role for the p110delta subunit of phosphatidylinositol 3-kinase in B cell development and activation
    Elizabeth Clayton
    Laboratory of Lymphocyte Signaling and Development, Molecular Immunology Programme, The Babraham Institute, Babraham, Cambridge CB2 4AT, United Kingdom
    J Exp Med 196:753-63. 2002
  2. pmc The p110delta isoform of PI 3-kinase negatively controls RhoA and PTEN
    Evangelia A Papakonstanti
    Ludwig Institute for Cancer Research, London, UK
    EMBO J 26:3050-61. 2007
  3. ncbi CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer
    Fabien Garcon
    Laboratory of Lymphocyte Signaling and Development, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
    Blood 111:1464-71. 2008
  4. pmc Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking
    Linda V Sinclair
    Department of Cell Biology and Immunology, University of Dundee, Dundee DD1 5EH, UK
    Nat Immunol 9:513-21. 2008
  5. ncbi Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice
    Klaus Okkenhaug
    Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK
    Science 297:1031-4. 2002
  6. ncbi Cutting edge: the phosphoinositide 3-kinase p110 delta is critical for the function of CD4+CD25+Foxp3+ regulatory T cells
    Daniel T Patton
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    J Immunol 177:6598-602. 2006
  7. pmc Essential, nonredundant role for the phosphoinositide 3-kinase p110delta in signaling by the B-cell receptor complex
    Shiann Tarng Jou
    Department of Biochemistry, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Mol Cell Biol 22:8580-91. 2002
  8. pmc PI3K p110delta regulates T-cell cytokine production during primary and secondary immune responses in mice and humans
    Dalya R Soond
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    Blood 115:2203-13. 2010
  9. ncbi p110delta, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes
    D Chantry
    ICOS Corporation, Bothell, Washington 98021, USA
    J Biol Chem 272:19236-41. 1997
  10. ncbi Role of the phosphoinositide 3-kinase p110delta in generation of type 2 cytokine responses and allergic airway inflammation
    Baher 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

Scientific Experts

Detail Information

Publications90

  1. pmc A crucial role for the p110delta subunit of phosphatidylinositol 3-kinase in B cell development and activation
    Elizabeth Clayton
    Laboratory of Lymphocyte Signaling and Development, Molecular Immunology Programme, The Babraham Institute, Babraham, Cambridge CB2 4AT, United Kingdom
    J Exp Med 196:753-63. 2002
    Mice lacking the p110delta catalytic subunit of phosphatidylinositol 3-kinase have reduced numbers of B1 and marginal zone B cells, reduced levels of serum immunoglobulins, respond poorly to immunization with type II thymus-independent ..
  2. pmc The p110delta isoform of PI 3-kinase negatively controls RhoA and PTEN
    Evangelia A Papakonstanti
    Ludwig Institute for Cancer Research, London, UK
    EMBO J 26:3050-61. 2007
    ..We report that the p110delta PI3K negatively regulates PTEN, through a pathway involving inhibition of RhoA...
  3. ncbi CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer
    Fabien Garcon
    Laboratory of Lymphocyte Signaling and Development, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
    Blood 111:1464-71. 2008
    ..imaging-based assay, we show that the PI3K activity at the T cell-APC contact area is dependent on the p110delta, but not the p110gamma, isoform of PI3K...
  4. pmc Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking
    Linda V Sinclair
    Department of Cell Biology and Immunology, University of Dundee, Dundee DD1 5EH, UK
    Nat Immunol 9:513-21. 2008
    ..CD62L downregulation occurred through ectodomain proteolysis and suppression of gene transcription. The p110delta subunit of PI(3)K controlled CD62L proteolysis through mitogen-activated protein kinases, whereas control of ..
  5. ncbi Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice
    Klaus Okkenhaug
    Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK
    Science 297:1031-4. 2002
    ..Mammals express three class IA catalytic subunits: p110alpha, p110beta, and p110delta. It is unclear to what extent these p110 isoforms have overlapping or distinct biological roles...
  6. ncbi Cutting edge: the phosphoinositide 3-kinase p110 delta is critical for the function of CD4+CD25+Foxp3+ regulatory T cells
    Daniel T Patton
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    J Immunol 177:6598-602. 2006
    ..Here we show that the proportions of Tregs in the spleen and lymph nodes of mice with inactive p110delta PI3K (p110deltaD910A/D910A) are reduced despite enhanced Treg selection in the thymus...
  7. pmc Essential, nonredundant role for the phosphoinositide 3-kinase p110delta in signaling by the B-cell receptor complex
    Shiann Tarng Jou
    Department of Biochemistry, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Mol Cell Biol 22:8580-91. 2002
    ..Germinal center formation in the spleen in response to antigen stimulation is disrupted. These results define a nonredundant signaling pathway(s) utilizing the delta isoform of p110 PI3K for the development and function of B cells...
  8. pmc PI3K p110delta regulates T-cell cytokine production during primary and secondary immune responses in mice and humans
    Dalya R Soond
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    Blood 115:2203-13. 2010
    We have previously described critical and nonredundant roles for the phosphoinositide 3-kinase p110delta during the activation and differentiation of naive T cells, and p110delta inhibitors are currently being developed for clinical use...
  9. ncbi p110delta, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes
    D Chantry
    ICOS Corporation, Bothell, Washington 98021, USA
    J Biol Chem 272:19236-41. 1997
    ..We have identified a novel p110 isoform of phosphatidylinositol 3-kinase from human leukocytes that we have termed p110delta. In addition, we have independently isolated p110delta from a mouse embryo library on the basis of its ability ..
  10. ncbi Role of the phosphoinositide 3-kinase p110delta in generation of type 2 cytokine responses and allergic airway inflammation
    Baher 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
    ..Here, we examined the effect of genetic inactivation of the hemopoietic cell-restricted PI3K isoform p110delta on systemic cytokine and chemokine responses and allergic airway inflammation...
  11. pmc Control of axonal growth and regeneration of sensory neurons by the p110delta PI 3-kinase
    Britta J Eickholt
    Medical Research Council Centre for Developmental Neurobiology, King s College London, London, United Kingdom
    PLoS ONE 2:e869. 2007
    ..Whereas most PI3Ks have a broad tissue distribution, the tyrosine kinase-linked p110delta isoform has previously been shown to be enriched in leukocytes...
  12. pmc Isoform-specific functions of phosphoinositide 3-kinases: p110 delta but not p110 gamma promotes optimal allergic responses in vivo
    Khaled 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
    The leukocyte-enriched p110gamma and p110delta isoforms of PI3K have been shown to control in vitro degranulation of mast cells induced by cross-linking of the high affinity receptor of IgE (FcepsilonRI)...
  13. pmc T cell receptor-induced phosphoinositide-3-kinase p110delta activity is required for T cell localization to antigenic tissue in mice
    Sarah J Jarmin
    Department of Immunology, Division of Medicine, Imperial College London, Hammersmith Campus, London, United Kingdom
    J Clin Invest 118:1154-64. 2008
    ..investigated whether signals downstream of TCR ligation mediated by the phosphoinositide-3-kinase (PI3K) subunit p110delta contributed to the regulation of these events...
  14. doi The p110 delta isoform of phosphatidylinositol 3-kinase controls the quality of secondary anti-Leishmania immunity by regulating expansion and effector function of memory T cell subsets
    Dong Liu
    Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada
    J Immunol 184:3098-105. 2010
    We showed previously that mice with an inactivating knockin mutation in the p110delta isoform of PI3K (referred to as p110delta(D910A) mice) displayed enhanced primary resistance to Leishmania major despite mounting paradoxically ..
  15. pmc Essential role of PI3Kdelta and PI3Kgamma in thymocyte survival
    Wojciech Swat
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA
    Blood 107:2415-22. 2006
    ..Surprisingly, genetic deletion of the p110delta and p110gamma catalytic subunits resulted in a dramatic reduction in thymus size, cellularity, and lack of ..
  16. ncbi Cutting edge: T cell development requires the combined activities of the p110gamma and p110delta catalytic isoforms of phosphatidylinositol 3-kinase
    Louise M C Webb
    Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham, Cambridge, United Kingdom
    J Immunol 175:2783-7. 2005
    ..birth (p110alpha-/- and p110beta-/-) or lack a significant T cell developmental phenotype (p110gamma-/- and p110delta-/-)...
  17. doi Leukemic challenge unmasks a requirement for PI3Kdelta in NK cell-mediated tumor surveillance
    Eva Zebedin
    Institute of Pharmacology, Medical University of Vienna MUW, Vienna, Austria
    Blood 112:4655-64. 2008
    ..We found that BCR/ABL(+) human leukemic cells express PI3Kdelta and therefore explored its impact on leukemia development...
  18. doi Distinct roles of class IA PI3K isoforms in primary and immortalised macrophages
    Evangelia A Papakonstanti
    Centre for Cell Signalling, Institute of Cancer, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK
    J Cell Sci 121:4124-33. 2008
    The class IA isoforms of phosphoinositide 3-kinase (p110alpha, p110beta and p110delta) often have non-redundant functions in a given cell type...
  19. ncbi Colony-stimulating factor-1 requires PI3-kinase-mediated metabolism for proliferation and survival in myeloid cells
    A W M Lee
    Department of Pharmacology, University of Michigan Medical School, 1150W Medical Center Dr, Ann Arbor, MI 48109, USA
    Cell Death Differ 13:1900-14. 2006
    ..This study identifies robust PI3-kinase activation as essential for optimal CSF-1-mediated mitogenesis in myeloid cells, in part through regulation of HKII and support of glycolysis...
  20. pmc The role of endothelial PI3Kgamma activity in neutrophil trafficking
    Kamal D Puri
    ICOS Corporation, Bothell, WA, USA
    Blood 106:150-7. 2005
    ..This alteration in adhesion was further augmented by a deficiency in p110delta, suggesting that the activity of both catalytic subunits is required for efficient capture of neutrophils by ..
  21. doi Role of phosphoinositide 3-kinase p110 delta in TLR4- and TLR9-mediated B cell cytokine production and differentiation
    Nyla Dil
    Department of Immunology, University of Manitoba, Winnipeg, MB, R3E 0W2, Canada
    Mol Immunol 46:1970-8. 2009
    ..Together, these results indicate that PI3K delta functions in influencing the type of B cell cytokine production and differentiation response induced by TLR-..
  22. ncbi PI 3-kinase p110beta: a new target for antithrombotic therapy
    Shaun P Jackson
    Australian Centre for Blood Diseases, Monash University, 6th Floor Burnet Building Alfred Medical Research and Education Precinct, Prahran, Victoria, Australia 3181
    Nat Med 11:507-14. 2005
    ..In vivo, these inhibitors eliminate occlusive thrombus formation but do not prolong bleeding time. These studies define PI3K p110beta as an important new target for antithrombotic therapy...
  23. doi Recycling endosome-dependent and -independent mechanisms for IL-10 secretion in LPS-activated macrophages
    A C Stanley
    Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia
    J Leukoc Biol 92:1227-39. 2012
    ..Thus, we show at least two post-Golgi pathways via which IL-10 is trafficked, ensuring its secretion from activated macrophages under different physiological conditions...
  24. doi Phosphoinositide 3-kinase p110 delta regulates natural antibody production, marginal zone and B-1 B cell function, and autoantibody responses
    Caylib A Durand
    Department of Microbiology and Immunology, Infection, Inflammation, and Immunity I 3 and CELL Research Groups, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
    J Immunol 183:5673-84. 2009
    ..Using IC87114, a highly selective inhibitor of p110delta enzymatic activity, we show that p110delta is important for murine B-1 and MZ B cells to respond to BCR ..
  25. doi Class IA phosphoinositide 3-kinase β and δ regulate neutrophil oxidase activation in response to Aspergillus fumigatus hyphae
    Keith B Boyle
    Inositide Laboratory, Babraham Institute, Cambridge CB22 3AT, United Kingdom
    J Immunol 186:2978-89. 2011
    ..These results start to define the signaling network controlling neutrophil ROS responses to A. fumigatus hyphae...
  26. ncbi p110delta is required for innate immunity to transplantable lymphomas
    A Saudemont
    Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham Research Campus, Cambridge, UK
    Biochem Soc Trans 35:183-5. 2007
    ..b>p110delta expression is restricted to leucocytes, where it plays central roles in lymphocyte development and signalling...
  27. ncbi Essential role for the p110delta phosphoinositide 3-kinase in the allergic response
    Khaled Ali
    Ludwig Institute for Cancer Research, 91 Riding House Street, London W1W 7BS, UK
    Nature 431:1007-11. 2004
    ..Here, we report that genetic or pharmacological inactivation of the p110delta isoform of PI(3)K in mast cells leads to defective SCF-mediated in vitro proliferation, adhesion and migration, ..
  28. pmc The p110 delta of PI3K plays a critical role in NK cell terminal maturation and cytokine/chemokine generation
    Hailong 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...
  29. ncbi Structural organization of the mouse phosphatidylinositol 3-kinase p110d gene
    E Clayton
    Lymphocyte Signaling and Development Laboratory, Babraham Institute, Babraham, Cambridge, CB2 4AT, United Kingdom
    Biochem Biophys Res Commun 280:1328-32. 2001
    ..Here we report the cloning, sequencing, and structural organization of the mouse p110delta gene from a murine 129/Sv genomic library. The p110delta gene consists of 22 exons and spans over 13 kb...
  30. ncbi The p110delta catalytic isoform of PI3K is a key player in NK-cell development and cytokine secretion
    Nayoung Kim
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    Blood 110:3202-8. 2007
    ..We show here that the catalytic isoform p110delta, not p110gamma, was required for interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and ..
  31. ncbi p110gamma and p110delta phosphoinositide 3-kinase signaling pathways synergize to control development and functions of murine NK cells
    Ilaria Tassi
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
    Immunity 27:214-27. 2007
    ..Here we showed that PI-3K class IB and class IA catalytic subunits, p110gamma and p110delta, played a crucial role in the development and functions of murine NK cells...
  32. ncbi The Pten/PI3K pathway governs the homeostasis of Valpha14iNKT cells
    Hiroyuki Kishimoto
    Department of Molecular Biology, Akita University School of Medicine, Hondo 1 1 1, Akita 0108 543, Japan
    Blood 109:3316-24. 2007
    ..Indeed, the effects of the Pten mutation require intact function of the PI3K subunits p110gamma and p110delta. In vivo, LckCrePten mice display reduced serum IFNgamma after alphaGalCer administration...
  33. doi p37δ is a new isoform of PI3K p110δ that increases cell proliferation and is overexpressed in tumors
    S Fransson
    Department of Medical and Clinical Genetics, Sahlgrenska Cancer Center, University of Gothenburg, Gothenburg, Sweden
    Oncogene 31:3277-86. 2012
    ..The PI3K catalytic subunit p110δ is encoded by PIK3CD and contains p85- and RAS-binding domains, and a kinase domain...
  34. pmc Neuregulin 1-ErbB4-PI3K signaling in schizophrenia and phosphoinositide 3-kinase-p110δ inhibition as a potential therapeutic strategy
    Amanda J Law
    Clinical Brain Disorders Branch, Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 109:12165-70. 2012
    ..increased expression of a PI3K-linked ErbB4 receptor (CYT-1) and the phosphoinositide 3-kinase subunit, p110δ (PIK3CD)...
  35. pmc E-selectin engages PSGL-1 and CD44 through a common signaling pathway to induce integrin alphaLbeta2-mediated slow leukocyte rolling
    Tadayuki Yago
    Cardiovascular Biology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA
    Blood 116:485-94. 2010
    ..Thus, E-selectin triggers common signals through distinct neutrophil glycoproteins to induce alpha(L)beta(2)-dependent slow rolling...
  36. doi Blockade of phosphatidylinositol 3-kinase PI3Kδ or PI3Kγ reduces IL-17 and ameliorates imiquimod-induced psoriasis-like dermatitis
    Anne Roller
    Rheumatology Research, Merck Serono S A, 1211 Geneva, Switzerland
    J Immunol 189:4612-20. 2012
    ..Taken together, these data indicate that PI3Kδ and/or PI3Kγ inhibitors should be considered for treating IL-17-driven diseases, such as psoriasis...
  37. doi p110δ phosphoinositide 3-kinase represses IgE switch by potentiating BCL6 expression
    Ting Ting Zhang
    Department of Immunology, University of Manitoba, Winnipeg, Manitoba R3E 0T5, Canada
    J Immunol 188:3700-8. 2012
    ....
  38. ncbi Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulation
    Lazaros 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...
  39. doi Autophagy regulates IL-23 secretion and innate T cell responses through effects on IL-1 secretion
    Celia Peral de Castro
    Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College, Dublin 2, Ireland
    J Immunol 189:4144-53. 2012
    ..These data demonstrate that autophagy has a potentially pivotal role to play in the induction and regulation of inflammatory responses by innate immune cells, largely driven by IL-1 and its consequential effects on IL-23 secretion...
  40. pmc Interleukin 15-mediated survival of natural killer cells is determined by interactions among Bim, Noxa and Mcl-1
    Nicholas D Huntington
    The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia
    Nat Immunol 8:856-63. 2007
    ..Thus, IL-15 regulates the survival of NK cells at multiple steps, with Bim and Noxa being key antagonists of Mcl-1, the critical survivor factor in this process...
  41. ncbi Inactivation of PI3Kgamma and PI3Kdelta distorts T-cell development and causes multiple organ inflammation
    Hong Ji
    Merck Serono S A, Geneva Research Center, Geneva, Switzerland
    Blood 110:2940-7. 2007
    Mice lacking both the p110gamma and p110delta isoforms display severe impairment of thymocyte development...
  42. doi The p110delta isoform of phosphatidylinositol 3-kinase controls susceptibility to Leishmania major by regulating expansion and tissue homing of regulatory T cells
    Dong Liu
    Department of Immunology, University of Manitoba, Winnipeg, Manitoba, Canada
    J Immunol 183:1921-33. 2009
    ..Mice with an inactivating knock-in mutation in the p110delta isoform of PI3K (referred to as p110delta(D910A)) show severely impaired T cell responses...
  43. doi The p110δ isoform of the kinase PI(3)K controls the subcellular compartmentalization of TLR4 signaling and protects from endotoxic shock
    Ezra 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...
  44. pmc Phosphoinositide 3-kinase-dependent inhibition of dendritic cell interleukin-12 production by Giardia lamblia
    Joel Désiré Kamda
    Department of Biology, Reiss 406, Georgetown University, Washington, DC 20057, USA
    Infect Immun 77:685-93. 2009
    ..These data suggest that this parasite actively interferes with host innate immunity, resulting in an immune response able to control the infection but devoid of strong inflammatory signals...
  45. pmc Human immunodeficiency virus type 1 Tat accelerates Kaposi sarcoma-associated herpesvirus Kaposin A-mediated tumorigenesis of transformed fibroblasts in vitro as well as in nude and immunocompetent mice
    Xiuying Chen
    Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, PR China
    Neoplasia 11:1272-84. 2009
    ....
  46. pmc CCL21 mediates CD4+ T-cell costimulation via a DOCK2/Rac-dependent pathway
    Kathrin Gollmer
    Theodor Kocher Institute, University of Bern, Freiestrasse 1, Bern, Switzerland
    Blood 114:580-8. 2009
    ..Kinase-dead PI3Kdelta(D910A/D910A) or PI3Kgamma-deficient TCR-tg CD4(+) T cells showed similar responsiveness to CCL21 costimulation ..
  47. pmc Phosphoinositide 3-kinase p110 beta regulates integrin alpha IIb beta 3 avidity and the cellular transmission of contractile forces
    Simone M Schoenwaelder
    Australian Centre for Blood Diseases, Monash University, Alfred Medical Research and Education Precinct, 89 Commercial Road, Melbourne, Victoria 3004, Australia
    J Biol Chem 285:2886-96. 2010
    ..These findings may provide new insight into the potential antithrombotic properties of PI3K p110 beta inhibitors...
  48. pmc Activity of any class IA PI3K isoform can sustain cell proliferation and survival
    Lazaros 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
    ..progenitor cells (which express all four class I PI3K isoforms), genetic inactivation of either p110alpha or p110delta did not affect cell proliferation or survival or sensitize to p110beta or p110gamma inactivation...
  49. pmc The large zinc finger protein ZAS3 is a critical modulator of osteoclastogenesis
    Shujun Liu
    Department of Internal Medicine, The Ohio State University, Columbus, Ohio, United States of America
    PLoS ONE 6:e17161. 2011
    ..In this report we demonstrated the role of ZAS3 in bone resorption by examining the signaling mechanisms involved in osteoclastogenesis...
  50. pmc The PI3K p110δ regulates expression of CD38 on regulatory T cells
    Daniel T Patton
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    PLoS ONE 6:e17359. 2011
    ..Therefore, CD38 can be used as a marker for Tregs with high suppressive activity and the impaired Treg function in p110δ(D910A) mice can in part be explained by the failure of CD38(high) cells to develop...
  51. doi VEGF-mediated PI3K class IA and PKC signaling in cardiomyogenesis and vasculogenesis of mouse embryonic stem cells
    Mohamed M Bekhite
    Department of Internal Medicine I, Cardiology Division, Friedrich Schiller University, 07743 Jena, Germany
    J Cell Sci 124:1819-30. 2011
    ..Akt downstream of PI3K is involved in both cardiomyogenesis and vasculogenesis, whereas PKC is involved only in vasculogenesis...
  52. doi Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible costimulator (CD278)
    Yenny Y Acosta
    Departamento de Medicina Celular y Molecular, Centro de Investigaciones Biologicas, CSIC, Ramiro de Maeztu, 9, 28040 Madrid, Spain
    Cell Mol Life Sci 68:3065-79. 2011
    ..Thus, p110α and p110δ are essential to optimal T cell activation, but their abundance and activity differentially tune up distinct ICOS signaling pathways...
  53. pmc Phosphatidylinositol 3-kinase-δ up-regulates L-type Ca2+ currents and increases vascular contractility in a mouse model of type 1 diabetes
    J F Pinho
    Department of Physiology and Biophysics, ICB, Federal University of Minas Gerais, Belo Horizonte, Brazil
    Br J Pharmacol 161:1458-71. 2010
    ..2). In the present work, we investigated the involvement of PI3K signalling in regulating Ca(2+) current through Ca(V) 1.2 (I(Ca,L) ) and vascular dysfunction in a mouse model of type I diabetes...
  54. pmc Phosphoinositide 3-kinase δ regulates membrane fission of Golgi carriers for selective cytokine secretion
    Pei Ching Low
    Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia
    J Cell Biol 190:1053-65. 2010
    ..These findings demonstrate a new function for p110δ as part of the membrane fission machinery required at the TGN for the selective trafficking and secretion of cytokines in macrophages...
  55. pmc Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism
    Andrew N Macintyre
    College of Life Sciences, Division of Cell Biology and Immunology, University of Dundee, Scotland, UK
    Immunity 34:224-36. 2011
    ..Akt is thus dispensable for metabolism, but the strength and duration of Akt activity dictates the CTL transcriptional program and determines CTL fate...
  56. doi Phosphoinositide 3-kinase activity in T cells regulates the magnitude of the germinal center reaction
    Julia Rolf
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    J Immunol 185:4042-52. 2010
    ..Our findings support a model in which the magnitude of the GC reaction is controlled by the activity of the PI3K pathway in T(FH) cells...
  57. pmc Dynamics of the phosphoinositide 3-kinase p110δ interaction with p85α and membranes reveals aspects of regulation distinct from p110α
    John E Burke
    Medical Research Council, Laboratory of Molecular Biology, Cambridge CB2 0QH, UK
    Structure 19:1127-37. 2011
    ..DXMS identified regions decreasing exposure at membranes and also regions gaining exposure, indicating loosening of interactions within the heterodimer at membranes...
  58. doi The catalytic PI3K isoforms p110gamma and p110delta contribute to B cell development and maintenance, transformation, and proliferation
    Sandra Beer-Hammer
    1 Abteilung für Pharmakologie und Experimentelle Therapie, Klinikum der Eberhard Karls Universität Tübingen, Wilhelmstrasse 56, D 72074 Tubingen, Germany Institute of Biochemistry and Molecular Biology II, University of Dusseldorf, Universitatsstrabetae 1, D 40225 Dusseldorf, Germany e mail
    J Leukoc Biol 87:1083-95. 2010
    ..mice revealed specific roles for the hematopoietically expressed PI3K catalytic subunits, p110gamma and p110delta, in development and function of T and B lymphocytes...
  59. doi B-cell responses to B-cell activation factor of the TNF family (BAFF) are impaired in the absence of PI3K delta
    Thomas Henley
    Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, UK
    Eur J Immunol 38:3543-8. 2008
    ..We therefore investigated the BAFF-mediated responses of B cells deficient for the PI3K catalytic subunit P110delta. We find that the loss of P110delta impairs the BAFF-mediated survival of cultured B cells demonstrating a ..
  60. ncbi The effect of deleting p110delta on the phenotype and function of PTEN-deficient B cells
    Michelle L Janas
    Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Babraham, Cambridge, United Kingdom
    J Immunol 180:739-46. 2008
    ..Deletion of the PI3K catalytic subunit p110delta leads to a severe reduction in B1 and marginal zone (MZ) B cells, whereas deletion of PTEN results in their ..
  61. 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...
  62. doi Interleukin 13 increases contractility of murine tracheal smooth muscle by a phosphoinositide 3-kinase p110delta-dependent mechanism
    Hanan S M Farghaly
    Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK
    Mol Pharmacol 73:1530-7. 2008
    ..and genetic approaches to demonstrate the role of signaling via the class I phosphoinositide 3-kinase p110delta isoform in IL-13-induced hyper-responsiveness of murine tracheal smooth muscle contractility in vitro...
  63. pmc Activation and function of the mTORC1 pathway in mast cells
    Mi Sun Kim
    Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA
    J Immunol 180:4586-95. 2008
    ..Specifically, the mTORC1 pathway may play a critical role in normal and dysregulated control of mast cell homeostasis...
  64. doi Phosphatidylinositol-3-kinase-atypical protein kinase C signaling is required for Wnt attraction and anterior-posterior axon guidance
    Alex M Wolf
    Committee on Developmental Biology, The University of Chicago, Chicago, Illinois 60637, USA
    J Neurosci 28:3456-67. 2008
    ..Therefore, we propose that atypical PKC signaling is required for Wnt-mediated A-P axon guidance and that PI3K can act as a switch to activate Wnt responsiveness during midline crossing...
  65. ncbi Phosphatidylinositol 3-kinase is required for the transcriptional activation of cyclin D2 in BCR activated primary mouse B lymphocytes
    Janet Glassford
    Cancer Research UK Laboratories, Department of Cancer Medicine, MRC Cyclotron Building, Imperial College London, Hammersmith Hospital, London, UK
    Eur J Immunol 35:2748-61. 2005
    ..D2, the p85alpha subunit of phosphatidylinositol 3-kinase (PI3K) or other components of the B cell signalosome, p110delta-null B cells fail to induce cyclin D2 and enter early G1 but not S phase of the cell cycle...
  66. ncbi Airway inflammation: chemokine-induced neutrophilia and the class I phosphoinositide 3-kinases
    Matthew J Thomas
    Novartis Institutes for BioMedical Research, Horsham, UK
    Eur J Immunol 35:1283-91. 2005
    ..No role for the delta isoform was demonstrated both in vitro and in vivo using PI3Kdelta kinase-dead knock-in mice...
  67. doi CD18-dependent activation of the neutrophil NADPH oxidase during phagocytosis of Escherichia coli or Staphylococcus aureus is regulated by class III but not class I or II PI3Ks
    Karen E Anderson
    Inositide Laboratory, Babraham Institute, Babraham Research Campus, Cambridge, United Kingdom
    Blood 112:5202-11. 2008
    ..This interaction does not, however, account for all the PI3K sensitivity of these responses, particularly the oxidase response to E coli, suggesting that additional mechanisms for PtdIns(3)P-regulation of the oxidase must exist...
  68. doi Regulation of adiponectin secretion by insulin and amino acids in 3T3-L1 adipocytes
    Regje M E Blumer
    Department of Endocrinology and Metabolism, Academic Medical Center, PO Box 22660, 1100 DD Amsterdam, The Netherlands
    Metabolism 57:1655-62. 2008
    ..In conclusion, adiponectin production is substrate driven. Phosphatidylinositol 3-kinase and an acidic lysosomal pH, but not amino acid-mediated mTOR signaling or lysosomal breakdown, are involved in adiponectin secretion...
  69. ncbi Mechanisms and implications of phosphoinositide 3-kinase delta in promoting neutrophil trafficking into inflamed tissue
    Kamal D Puri
    ICOS, Bothell, WA 98021, USA
    Blood 103:3448-56. 2004
    ..Specifically, administration of the selective inhibitor of PI3K delta, IC87114, to animals reduced neutrophil tethering to and increased rolling velocities on cytokine-activated ..
  70. ncbi Human osteoclast-like cells are formed from peripheral blood mononuclear cells in a coculture with SaOS-2 cells transfected with the parathyroid hormone (PTH)/PTH-related protein receptor gene
    K Matsuzaki
    Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan
    Endocrinology 140:925-32. 1999
    ..This coculture model will be useful for investigating the abnormalities ofosteoclast differentiation and function in human metabolic bone diseases...
  71. ncbi P-selectin primes leukocyte integrin activation during inflammation
    Hai bo Wang
    Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Graduate School of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
    Nat Immunol 8:882-92. 2007
    ..Src kinases phosphorylated Nef-associated factor 1, which recruited the phosphoinositide-3-OH kinase p85-p110delta heterodimer and resulted in activation of leukocyte integrins...
  72. ncbi 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 cells
    Antonio Bilancio
    Ludwig Institute for Cancer Research, 91 Riding House Street, London, W1W 7BS, United Kingdom
    Blood 107:642-50. 2006
    Mouse gene-targeting studies have documented a central role of the p110delta isoform of phosphoinositide 3-kinase (PI3K) in B-cell development and function...
  73. ncbi The p110delta subunit of phosphoinositide 3-kinase is required for the lipopolysaccharide response of mouse B cells
    B J Hebeis
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Babraham Research Campus, Cambridge CB2 4AT, UK
    Biochem Soc Trans 32:789-91. 2004
    PI3K (phosphoinositide 3-kinase) I(A) family members contain a regulatory subunit and a catalytic subunit. The p110delta catalytic subunit is expressed predominantly in haematopoietic cells...
  74. ncbi Selective role of PI3K delta in neutrophil inflammatory responses
    Chanchal Sadhu
    ICOS Corporation, 22021 20th Avenue SE, Bothell, WA 98021, USA
    Biochem Biophys Res Commun 308:764-9. 2003
    ..We have developed a novel series of PI3K inhibitors that is selective for PI3K delta, an isoform expressed predominantly in hematopoietic cells...
  75. ncbi Requirement for phosphoinositide 3-kinase p110delta signaling in B cell antigen receptor-mediated antigen presentation
    Monther M Al-Alwan
    Department of Immunology, University of Manitoba, Winnipeg, Canada
    J Immunol 178:2328-35. 2007
    ..PI3Ks are critical signaling enzymes controlling many cellular processes, with the p110delta isoform playing a critical role in BCR signaling...
  76. ncbi Identification of a unique co-operative phosphoinositide 3-kinase signaling mechanism regulating integrin alpha IIb beta 3 adhesive function in platelets
    Simone M Schoenwaelder
    Australian Centre for Blood Diseases, Monash University, Alfred Medical Research and Education Precinct AMREP, 89 Commercial Road, Melbourne, Victoria, Australia
    J Biol Chem 282:28648-58. 2007
    ..These findings have potentially important implications for the rationale design of novel antiplatelet therapies targeting PI 3-kinase signaling pathways...
  77. pmc p110gamma and p110delta isoforms of phosphoinositide 3-kinase differentially regulate natural killer cell migration in health and disease
    Aurore Saudemont
    Laboratory of Lymphocyte Signalling, The Babraham Institute, CB22 3AT Cambridge, United Kingdom
    Proc Natl Acad Sci U S A 106:5795-800. 2009
    ..Phosphoinositide-3 kinases (PI3K) control cell motility and the p110gamma and p110delta isoforms are mostly expressed in leukocytes, where they transduce signals downstream of G protein coupled ..
  78. pmc Regulation of p110delta PI 3-kinase gene expression
    Klaartje 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 ..
  79. doi Genetic or pharmaceutical blockade of p110delta phosphoinositide 3-kinase enhances IgE production
    Ting Ting Zhang
    CIHR National Training Program in Allergy and Asthma Research, University of Manitoba, Winnipeg, Manitoba, Canada
    J Allergy Clin Immunol 122:811-819.e2. 2008
    ..Signals generated by the p110delta PI3K isoform play critical roles in signaling through antigen and cytokine receptors and were shown to be ..
  80. pmc Phosphoinositide 3-kinases gamma and delta, linkers of coordinate C5a receptor-Fcgamma receptor activation and immune complex-induced inflammation
    Stephanie Konrad
    Molecular Immunology Research Unit, Clinic for Immunology and Rheumatology, Hanover Medical School, Hanover, Germany
    J Biol Chem 283:33296-303. 2008
    ..Notably, however, C5a production occurred normally in PI3Kgamma(-/-) mice but was impaired in PI3Kdelta(-/-) mice. Consequently, class IA PI3Kdelta deficiency caused resistance to acute IC lung injury...
  81. pmc TRPM7 ion channels are required for sustained phosphoinositide 3-kinase signaling in lymphocytes
    Jaya Sahni
    Department of Pediatrics, University of Washington and Seattle Children s Hospital Research Institute, Seattle, WA 98101, USA
    Cell Metab 8:84-93. 2008
    ....
  82. doi Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration
    Mariona Graupera
    Centre for Cell Signalling, Institute of Cancer, Queen Mary, University of London, Charterhouse Square, London EC1M 6BQ, UK
    Nature 453:662-6. 2008
    ..IA PI3K isoforms couple to tyrosine kinases and consist of a p110 catalytic subunit (p110alpha, p110beta or p110delta), constitutively bound to one of five distinct p85 regulatory subunits...
  83. pmc Role of PI3Kdelta and PI3Kgamma in inflammatory arthritis and tissue localization of neutrophils
    Tara M Randis
    Department of Pediatrics, Columbia University Medical Center, New York, NY 10032, USA
    Eur J Immunol 38:1215-24. 2008
    The p110delta isoform of class I phosphoinositide 3-kinase (PI3K) plays a major role in B cell receptor signaling, while its p110gamma counterpart is thought to predominate in leukocyte chemotaxis...
  84. pmc Thymic development beyond beta-selection requires phosphatidylinositol 3-kinase activation by CXCR4
    Michelle L Janas
    Laboratory of Lymphocyte Signaling and Development, The Babraham Institute, Babraham, Cambridge, CB22 3AT England, UK
    J Exp Med 207:247-61. 2010
    ..development requires phosphatidylinositol 3-kinase (PI3K) signaling with contributions from both the class IA, p110delta, and class IB, p110gamma catalytic subunits...
  85. pmc Role of the p110delta PI 3-kinase in integrin and ITAM receptor signalling in platelets
    Yotis 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
    We have investigated the function of the p110delta catalytic subunit of phosphoinositide 3-kinase (PI 3-kinase) in platelets using p110delta knock-out (p110delta(-/-)) mice and p110delta knock-in (p110delta(D910A/D910A)) mice, which ..
  86. ncbi The p110delta isoform of phosphoinositide 3-kinase controls clonal expansion and differentiation of Th cells
    Klaus Okkenhaug
    Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge, United Kingdom
    J Immunol 177:5122-8. 2006
    ..We previously reported that a kinase-inactivating mutation (D910A) in the p110delta isoform of PI3K results in normal T cell development, but impaired TCR-stimulated cell proliferation in vitro...
  87. ncbi The PI3K p110delta is required for down-regulation of RAG expression in immature B cells
    Miriam Llorian
    Laboratory of Lymphocyte Signalling and Development, The Babraham Institute, Cambridge, United Kingdom
    J Immunol 178:1981-5. 2007
    ..We demonstrate that immature B cells from mice deficient in the PI3K catalytic subunit p110delta fail to suppress RAG expression and inappropriately recombine kappa and lambda LC loci...
  88. ncbi Role of ERas in promoting tumour-like properties in mouse embryonic stem cells
    Kazutoshi Takahashi
    Laboratory of Animal Molecular Technology, Research and Education Center for Genetic Information, Nara Institute of Science and Technology, Ikoma, Nara 630 0192, Japan
    Nature 423:541-5. 2003
    ..We conclude that the transforming oncogene ERas is important in the tumour-like growth properties of ES cells...
  89. ncbi The PI3K inhibitor arsenal: choose your weapon!
    Tom Crabbe
    UCB Celltech, Slough, UK
    Trends Biochem Sci 32:450-6. 2007
    ..However, challenges remain for the efforts to pharmacologically target this enzyme family in a successful manner...
  90. ncbi Phosphatidylinositol 3-kinase association with the osteoclast cytoskeleton, and its involvement in osteoclast attachment and spreading
    P T Lakkakorpi
    Department of Bone Biology and Osteoporosis Research, Merck Research Laboratory, West Point, Pennsylvania 19486, USA
    Exp Cell Res 237:296-306. 1997
    ..Finally, PI3-kinase coimmunoprecipitated with alpha v beta 3 integrin from osteoclasts...

Research Grants22

  1. Mechanisms of RelA Activation in Cancer
    Paul Chiao; Fiscal Year: 2009
    ..The proposed study will fill in the gaps in our understanding of the molecular mechanisms of tumorigenesis in pancreatic cells. ..
  2. Validation of potential early diagnostic and prognostic markers for pancreatic ca
    Paul Chiao; Fiscal Year: 2007
    ....
  3. Mechanisms of Tumorigenesis in Pancreatic Epithelial Cells
    Paul Chiao; Fiscal Year: 2009
    ..abstract_text> ..
  4. Mechanisms of RelA Activation in Cancer
    Paul J Chiao; Fiscal Year: 2010
    ..Most importantly, this study may discover novel molecular targets for improving the treatment for pancreatic cancer. ..
  5. Function and Regulation Mechanisms of Polo-like Kinase 3 in Pancreatic Cancer
    Paul J Chiao; Fiscal Year: 2010
    ....
  6. Mechanism of RelA activation in Pancreatic cancer
    Paul Chiao; Fiscal Year: 2006
    ..abstract_text> ..
  7. Phosphoinositide 3-Kinase Function in Lymphocytes
    David Fruman; Fiscal Year: 2006
    ..Biochemical assays will be used to analyze signaling in purified T cells. These studies will increase our understanding of PI3K signaling, a central control point in lymphocyte proliferation. ..
  8. PI3K Signaling in Single Lymphocytes Analyzed by LMS
    David Fruman; Fiscal Year: 2005
    ..Our second aim is to apply this technology to address the role of the PI3K regulatory isoform p85alpha in activation of different downstream signaling molecules. ..
  9. THE ROLE OF RE1A IN HUMAN ADENOCARCINOMA OF PANCREAS
    Paul Chiao; Fiscal Year: 2002
    ..The studies may lead to the development of specific inhibitors of Rel/NFkB for use in novel therapies for pancreatic cancers. ..
  10. Mechanisms of Overexpressed TrkB in Inducing Pancreatic Cancer Metastasis
    Paul J Chiao; Fiscal Year: 2010
    ..The proposed study will fill in the gaps in our understanding of the molecular mechanisms of human pancreatic cancer metastasis by studying the novel signaling pathways mediated by TrkBT1 overexpression. ..