Pik3cd

Summary

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

Top Publications

  1. Clayton E, Bardi G, Bell S, Chantry D, Downes C, Gray A, et al. A crucial role for the p110delta subunit of phosphatidylinositol 3-kinase in B cell development and activation. J Exp Med. 2002;196:753-63 pubmed
    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. Papakonstanti E, Ridley A, Vanhaesebroeck B. The p110delta isoform of PI 3-kinase negatively controls RhoA and PTEN. EMBO J. 2007;26:3050-61 pubmed
    ..We report that the p110delta PI3K negatively regulates PTEN, through a pathway involving inhibition of RhoA...
  3. Garcon F, Patton D, Emery J, Hirsch E, Rottapel R, Sasaki T, et al. CD28 provides T-cell costimulation and enhances PI3K activity at the immune synapse independently of its capacity to interact with the p85/p110 heterodimer. Blood. 2008;111:1464-71 pubmed
    ..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. Dil N, Marshall A. Role of phosphoinositide 3-kinase p110 delta in TLR4- and TLR9-mediated B cell cytokine production and differentiation. Mol Immunol. 2009;46:1970-8 pubmed publisher
    ..Together, these results indicate that PI3K delta functions in influencing the type of B cell cytokine production and differentiation response induced by TLR-..
  5. Kishimoto H, Ohteki T, Yajima N, Kawahara K, Natsui M, Kawarasaki S, et al. The Pten/PI3K pathway governs the homeostasis of Valpha14iNKT cells. Blood. 2007;109:3316-24 pubmed
    ..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...
  6. Clayton E, McAdam S, Coadwell J, Chantry D, Turner M. Structural organization of the mouse phosphatidylinositol 3-kinase p110d gene. Biochem Biophys Res Commun. 2001;280:1328-32 pubmed
    ..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...
  7. Okkenhaug K, Bilancio A, Farjot G, Priddle H, Sancho S, Peskett E, et al. Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice. Science. 2002;297:1031-4 pubmed
    ..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...
  8. Jou S, Carpino N, Takahashi Y, Piekorz R, Chao J, Carpino N, et al. Essential, nonredundant role for the phosphoinositide 3-kinase p110delta in signaling by the B-cell receptor complex. Mol Cell Biol. 2002;22:8580-91 pubmed
    ..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. ..
  9. Saudemont A, Okkenhaug K, Colucci F. p110delta is required for innate immunity to transplantable lymphomas. Biochem Soc Trans. 2007;35:183-5 pubmed
    ..b>p110delta expression is restricted to leucocytes, where it plays central roles in lymphocyte development and signalling...

More Information

Publications78

  1. Putz E, Prchal Murphy M, Simma O, Forster F, Koenig X, Stockinger H, et al. PI3K? is essential for tumor clearance mediated by cytotoxic T lymphocytes. PLoS ONE. 2012;7:e40852 pubmed publisher
    ..Our results demonstrate that CTL-mediated tumor surveillance is severely impaired in the absence of PI3K? and predict that impaired immunosurveillance may limit the effectiveness of PI3K? inhibitors in long-term treatment. ..
  2. Nashed B, Zhang T, Al Alwan M, Srinivasan G, Halayko A, Okkenhaug K, et al. Role of the phosphoinositide 3-kinase p110delta in generation of type 2 cytokine responses and allergic airway inflammation. Eur J Immunol. 2007;37:416-24 pubmed
    ..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...
  3. Jackson S, Schoenwaelder S, Goncalves I, Nesbitt W, Yap C, Wright C, et al. PI 3-kinase p110beta: a new target for antithrombotic therapy. Nat Med. 2005;11:507-14 pubmed
    ..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. ..
  4. Sinclair L, Finlay D, Feijoo C, Cornish G, Gray A, Ager A, et al. Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking. Nat Immunol. 2008;9:513-21 pubmed publisher
    ..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. Kim N, Saudemont A, Webb L, Camps M, Ruckle T, Hirsch E, et al. The p110delta catalytic isoform of PI3K is a key player in NK-cell development and cytokine secretion. Blood. 2007;110:3202-8 pubmed
    ..We show here that the catalytic isoform p110delta, not p110gamma, was required for interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and ..
  6. Webb L, Vigorito E, Wymann M, Hirsch E, Turner M. Cutting edge: T cell development requires the combined activities of the p110gamma and p110delta catalytic isoforms of phosphatidylinositol 3-kinase. J Immunol. 2005;175:2783-7 pubmed
    ..birth (p110alpha-/- and p110beta-/-) or lack a significant T cell developmental phenotype (p110gamma-/- and p110delta-/-)...
  7. Rolf J, Bell S, Kovesdi D, Janas M, Soond D, Webb L, et al. Phosphoinositide 3-kinase activity in T cells regulates the magnitude of the germinal center reaction. J Immunol. 2010;185:4042-52 pubmed publisher
    ..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...
  8. Tassi I, Cella M, Gilfillan S, Turnbull I, Diacovo T, Penninger J, et al. p110gamma and p110delta phosphoinositide 3-kinase signaling pathways synergize to control development and functions of murine NK cells. Immunity. 2007;27:214-27 pubmed
    ..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...
  9. Aksoy E, Taboubi S, Torres D, Delbauve S, Hachani A, Whitehead M, et al. The p110δ isoform of the kinase PI(3)K controls the subcellular compartmentalization of TLR4 signaling and protects from endotoxic shock. Nat Immunol. 2012;13:1045-1054 pubmed publisher
    ..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. ..
  10. Jarmin S, David R, Ma L, Chai J, Dewchand H, Takesono A, et al. T cell receptor-induced phosphoinositide-3-kinase p110delta activity is required for T cell localization to antigenic tissue in mice. J Clin Invest. 2008;118:1154-64 pubmed publisher
    ..investigated whether signals downstream of TCR ligation mediated by the phosphoinositide-3-kinase (PI3K) subunit p110delta contributed to the regulation of these events...
  11. Eickholt B, Ahmed A, Davies M, Papakonstanti E, Pearce W, Starkey M, et al. Control of axonal growth and regeneration of sensory neurons by the p110delta PI 3-kinase. PLoS ONE. 2007;2:e869 pubmed
    ..Whereas most PI3Ks have a broad tissue distribution, the tyrosine kinase-linked p110delta isoform has previously been shown to be enriched in leukocytes...
  12. Zebedin E, Simma O, Schuster C, Putz E, Fajmann S, Warsch W, et al. Leukemic challenge unmasks a requirement for PI3Kdelta in NK cell-mediated tumor surveillance. Blood. 2008;112:4655-64 pubmed publisher
    ..We found that BCR/ABL(+) human leukemic cells express PI3Kdelta and therefore explored its impact on leukemia development...
  13. Ali K, Bilancio A, Thomas M, Pearce W, Gilfillan A, Tkaczyk C, et al. Essential role for the p110delta phosphoinositide 3-kinase in the allergic response. Nature. 2004;431:1007-11 pubmed
    ..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, ..
  14. Chantry D, Vojtek A, Kashishian A, Holtzman D, Wood C, Gray P, et al. p110delta, a novel phosphatidylinositol 3-kinase catalytic subunit that associates with p85 and is expressed predominantly in leukocytes. J Biol Chem. 1997;272:19236-41 pubmed
    ..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 ..
  15. Swat W, Montgrain V, Doggett T, Douangpanya J, Puri K, Vermi W, et al. Essential role of PI3Kdelta and PI3Kgamma in thymocyte survival. Blood. 2006;107:2415-22 pubmed
    ..We now report that PI3Kdelta, in conjunction with PI3Kgamma, is required for thymocyte survival and ultimately for T-cell production...
  16. Graupera M, Guillermet Guibert J, Foukas L, Phng L, Cain R, Salpekar A, et al. Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration. Nature. 2008;453:662-6 pubmed publisher
    ..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...
  17. Puri K, Doggett T, Huang C, Douangpanya J, Hayflick J, Turner M, et al. The role of endothelial PI3Kgamma activity in neutrophil trafficking. Blood. 2005;106:150-7 pubmed
    ..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 ..
  18. Soond D, Bjørgo E, Moltu K, Dale V, Patton D, Torgersen K, et al. PI3K p110delta regulates T-cell cytokine production during primary and secondary immune responses in mice and humans. Blood. 2010;115:2203-13 pubmed publisher
    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...
  19. Foukas L, Claret M, Pearce W, Okkenhaug K, Meek S, Peskett E, et al. Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulation. Nature. 2006;441:366-70 pubmed
    ..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. ..
  20. Papakonstanti E, Zwaenepoel O, Bilancio A, Burns E, Nock G, Houseman B, et al. Distinct roles of class IA PI3K isoforms in primary and immortalised macrophages. J Cell Sci. 2008;121:4124-33 pubmed publisher
    The class IA isoforms of phosphoinositide 3-kinase (p110alpha, p110beta and p110delta) often have non-redundant functions in a given cell type...
  21. Liu D, Zhang T, Marshall A, Okkenhaug K, Vanhaesebroeck B, Uzonna J. The p110delta isoform of phosphatidylinositol 3-kinase controls susceptibility to Leishmania major by regulating expansion and tissue homing of regulatory T cells. J Immunol. 2009;183:1921-33 pubmed publisher
    ..Mice with an inactivating knock-in mutation in the p110delta isoform of PI3K (referred to as p110delta(D910A)) show severely impaired T cell responses...
  22. Patton D, Garden O, Pearce W, Clough L, Monk C, Leung E, et al. Cutting edge: the phosphoinositide 3-kinase p110 delta is critical for the function of CD4+CD25+Foxp3+ regulatory T cells. J Immunol. 2006;177:6598-602 pubmed
    ..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...
  23. Ali K, Camps M, Pearce W, Ji H, Ruckle T, Kuehn N, et al. Isoform-specific functions of phosphoinositide 3-kinases: p110 delta but not p110 gamma promotes optimal allergic responses in vivo. J Immunol. 2008;180:2538-44 pubmed
    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)...
  24. Guo H, Samarakoon A, Vanhaesebroeck B, Malarkannan S. The p110 delta of PI3K plays a critical role in NK cell terminal maturation and cytokine/chemokine generation. J Exp Med. 2008;205:2419-35 pubmed publisher
    ..These results reveal a previously unrecognized role of PI3K-p110 delta in NK cell development and effector functions. ..
  25. Liu D, Uzonna J. 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. J Immunol. 2010;184:3098-105 pubmed publisher
    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 ..
  26. Kulkarni S, Sitaru C, Jakus Z, Anderson K, Damoulakis G, Davidson K, et al. PI3Kβ plays a critical role in neutrophil activation by immune complexes. Sci Signal. 2011;4:ra23 pubmed publisher
    ..These results define PI3Kβ as a potential therapeutic target in inflammatory disease. ..
  27. Boyle K, Gyori D, Sindrilaru A, Scharffetter Kochanek K, Taylor P, Mócsai A, et al. Class IA phosphoinositide 3-kinase β and δ regulate neutrophil oxidase activation in response to Aspergillus fumigatus hyphae. J Immunol. 2011;186:2978-89 pubmed publisher
    ..These results start to define the signaling network controlling neutrophil ROS responses to A. fumigatus hyphae. ..
  28. Foukas L, Berenjeno I, Gray A, Khwaja A, Vanhaesebroeck B. Activity of any class IA PI3K isoform can sustain cell proliferation and survival. Proc Natl Acad Sci U S A. 2010;107:11381-6 pubmed publisher
    ..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...
  29. Puri K, Doggett T, Douangpanya J, Hou Y, Tino W, Wilson T, et al. Mechanisms and implications of phosphoinositide 3-kinase delta in promoting neutrophil trafficking into inflamed tissue. Blood. 2004;103:3448-56 pubmed
    ..Specifically, administration of the selective inhibitor of PI3K delta, IC87114, to animals reduced neutrophil tethering to and increased rolling velocities on cytokine-activated ..
  30. Okkenhaug K, Patton D, Bilancio A, Garcon F, Rowan W, Vanhaesebroeck B. The p110delta isoform of phosphoinositide 3-kinase controls clonal expansion and differentiation of Th cells. J Immunol. 2006;177:5122-8 pubmed
    ..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...
  31. Macintyre A, Finlay D, Preston G, Sinclair L, Waugh C, Tamas P, et al. Protein kinase B controls transcriptional programs that direct cytotoxic T cell fate but is dispensable for T cell metabolism. Immunity. 2011;34:224-36 pubmed publisher
    ..Akt is thus dispensable for metabolism, but the strength and duration of Akt activity dictates the CTL transcriptional program and determines CTL fate. ..
  32. Ji H, Rintelen F, Waltzinger C, Bertschy Meier D, Bilancio A, Pearce W, et al. Inactivation of PI3Kgamma and PI3Kdelta distorts T-cell development and causes multiple organ inflammation. Blood. 2007;110:2940-7 pubmed
    Mice lacking both the p110gamma and p110delta isoforms display severe impairment of thymocyte development...
  33. Garcon F, Okkenhaug K. PI3K? promotes CD4(+) T-cell interactions with antigen-presenting cells by increasing LFA-1 binding to ICAM-1. Immunol Cell Biol. 2016;94:486-95 pubmed publisher
    ..These results establish a link between PI3K activity, cytoskeletal changes and integrin binding and help explain the impaired T-cell-dependent immune responses in PI3K?-deficient mice. ..
  34. Kamda J, Singer S. Phosphoinositide 3-kinase-dependent inhibition of dendritic cell interleukin-12 production by Giardia lamblia. Infect Immun. 2009;77:685-93 pubmed publisher
    ..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. ..
  35. Kok K, Nock G, Verrall E, Mitchell M, Hommes D, Peppelenbosch M, et al. Regulation of p110delta PI 3-kinase gene expression. PLoS ONE. 2009;4:e5145 pubmed publisher
    ..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 ..
  36. Crabbe T, Welham M, Ward S. The PI3K inhibitor arsenal: choose your weapon!. Trends Biochem Sci. 2007;32:450-6 pubmed
    ..However, challenges remain for the efforts to pharmacologically target this enzyme family in a successful manner. ..
  37. Attridge K, Kenefeck R, Wardzinski L, Qureshi O, Wang C, Manzotti C, et al. IL-21 promotes CD4 T cell responses by phosphatidylinositol 3-kinase-dependent upregulation of CD86 on B cells. J Immunol. 2014;192:2195-201 pubmed publisher
    ..These data pinpoint CD86 upregulation as an additional mechanism by which IL-21 can elicit immunomodulatory effects. ..
  38. Schoenwaelder S, Ono A, Nesbitt W, Lim J, Jarman K, Jackson S. Phosphoinositide 3-kinase p110 beta regulates integrin alpha IIb beta 3 avidity and the cellular transmission of contractile forces. J Biol Chem. 2010;285:2886-96 pubmed publisher
    ..These findings may provide new insight into the potential antithrombotic properties of PI3K p110 beta inhibitors. ..
  39. GOODWIN C, Li X, Mali R, Chan G, Kang M, Liu Z, et al. PI3K p110? uniquely promotes gain-of-function Shp2-induced GM-CSF hypersensitivity in a model of JMML. Blood. 2014;123:2838-42 pubmed publisher
  40. Wang H, Wang J, Zhang L, Geng Z, Xu W, Xu T, et al. P-selectin primes leukocyte integrin activation during inflammation. Nat Immunol. 2007;8:882-92 pubmed
    ..Src kinases phosphorylated Nef-associated factor 1, which recruited the phosphoinositide-3-OH kinase p85-p110delta heterodimer and resulted in activation of leukocyte integrins...
  41. Randis T, Puri K, Zhou H, Diacovo T. Role of PI3Kdelta and PI3Kgamma in inflammatory arthritis and tissue localization of neutrophils. Eur J Immunol. 2008;38:1215-24 pubmed publisher
    ..We now demonstrate that PI3Kdelta blockade is effective in treating an autoimmune disorder in which neutrophil infiltration is required for tissue ..
  42. Patton D, Wilson M, Rowan W, Soond D, Okkenhaug K. The PI3K p110δ regulates expression of CD38 on regulatory T cells. PLoS ONE. 2011;6:e17359 pubmed publisher
    ..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. ..
  43. Matsuzaki K, Katayama K, Takahashi Y, Nakamura I, Udagawa N, Tsurukai T, et al. 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. Endocrinology. 1999;140:925-32 pubmed
    ..This coculture model will be useful for investigating the abnormalities ofosteoclast differentiation and function in human metabolic bone diseases. ..
  44. Ramadani F, Bolland D, Garcon F, Emery J, Vanhaesebroeck B, Corcoran A, et al. The PI3K isoforms p110alpha and p110delta are essential for pre-B cell receptor signaling and B cell development. Sci Signal. 2010;3:ra60 pubmed publisher
    ..Previous work has revealed a key role for the p110delta isoform of phosphatidylinositol 3-kinase (PI3K) in agonist-induced BCR signaling; however, early B cell ..
  45. Blumer R, van Roomen C, Meijer A, Houben Weerts J, Sauerwein H, Dubbelhuis P. Regulation of adiponectin secretion by insulin and amino acids in 3T3-L1 adipocytes. Metabolism. 2008;57:1655-62 pubmed publisher
    ..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. ..
  46. Lee A, States D. Colony-stimulating factor-1 requires PI3-kinase-mediated metabolism for proliferation and survival in myeloid cells. Cell Death Differ. 2006;13:1900-14 pubmed
    ..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. ..
  47. Farghaly H, Blagbrough I, Medina Tato D, Watson M. Interleukin 13 increases contractility of murine tracheal smooth muscle by a phosphoinositide 3-kinase p110delta-dependent mechanism. Mol Pharmacol. 2008;73:1530-7 pubmed publisher
    ..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...
  48. Peral de Castro C, Jones S, Ní Cheallaigh C, Hearnden C, Williams L, Winter J, et al. Autophagy regulates IL-23 secretion and innate T cell responses through effects on IL-1 secretion. J Immunol. 2012;189:4144-53 pubmed publisher
    ..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. ..
  49. Pinho J, Medeiros M, Capettini L, Rezende B, Campos P, Andrade S, et al. Phosphatidylinositol 3-kinase-? up-regulates L-type Ca2+ currents and increases vascular contractility in a mouse model of type 1 diabetes. Br J Pharmacol. 2010;161:1458-71 pubmed publisher
    ..Blockade of PI3K? may represent a novel therapeutic approach to treat vascular dysfunction in diabetic patients. ..
  50. Low P, Manzanero S, Mohannak N, Narayana V, Nguyen T, Kvaskoff D, et al. PI3K? inhibition reduces TNF secretion and neuroinflammation in a mouse cerebral stroke model. Nat Commun. 2014;5:3450 pubmed publisher
    ..These data identify PI3K? as a potential therapeutic target in ischaemic stroke. ..
  51. Glassford J, Vigorito E, Soeiro I, Madureira P, Zoumpoulidou G, Brosens J, et al. Phosphatidylinositol 3-kinase is required for the transcriptional activation of cyclin D2 in BCR activated primary mouse B lymphocytes. Eur J Immunol. 2005;35:2748-61 pubmed
    ..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...
  52. Gayral S, Garnotel R, Castaing Berthou A, Blaise S, Fougerat A, Berge E, et al. Elastin-derived peptides potentiate atherosclerosis through the immune Neu1-PI3K? pathway. Cardiovasc Res. 2014;102:118-27 pubmed publisher
    ..Altogether, this work identifies EP as an enhancer of atherogenesis and defines the Neuraminidase 1/PI3K? signalling pathway as a key mediator of this function in vitro and in vivo. ..
  53. Mauro C, Smith J, Cucchi D, Coe D, Fu H, Bonacina F, et al. Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4+ T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals. Cell Metab. 2017;25:593-609 pubmed publisher
  54. Al Alwan M, Okkenhaug K, Vanhaesebroeck B, Hayflick J, Marshall A. Requirement for phosphoinositide 3-kinase p110delta signaling in B cell antigen receptor-mediated antigen presentation. J Immunol. 2007;178:2328-35 pubmed
    ..PI3Ks are critical signaling enzymes controlling many cellular processes, with the p110delta isoform playing a critical role in BCR signaling...
  55. Janas M, Turner M. Interaction of Ras with p110? is required for thymic ?-selection in the mouse. J Immunol. 2011;187:4667-75 pubmed publisher
    ..Uncoupling Ras from p110? provides unambiguous identification of a Ras interaction required for thymic ?-selection. ..
  56. Mothes B, Bucher K, Ammon Treiber S, Schwab M, Piekorz R, Hirsch E, et al. p110?/? Double-Deficiency Induces Eosinophilia and IgE Production but Protects from OVA-Induced Airway Inflammation. PLoS ONE. 2016;11:e0159310 pubmed publisher
    ..We conclude that increased levels of eosinophils and IgE in p110?/?-/- mice do not abolish the protective effect of p110?/?-deficiency against OVA-induced allergic airway inflammation. ..
  57. Zotes T, Spada R, Mulens V, Pérez Yagüe S, Sorzano C, Okkenhaug K, et al. PI3K p110? is expressed by gp38(-)CD31(+) and gp38(+)CD31(+) spleen stromal cells and regulates their CCL19, CCL21, and LT?R mRNA levels. PLoS ONE. 2013;8:e72960 pubmed publisher
  58. Zheng L, Xing L, Zeng C, Wu T, Gui Y, Li W, et al. Inactivation of PI3Kδ induces vascular injury and promotes aneurysm development by upregulating the AP-1/MMP-12 pathway in macrophages. Arterioscler Thromb Vasc Biol. 2015;35:368-77 pubmed publisher
  59. Low P, Misaki R, Schroder K, Stanley A, Sweet M, Teasdale R, et al. Phosphoinositide 3-kinase ? regulates membrane fission of Golgi carriers for selective cytokine secretion. J Cell Biol. 2010;190:1053-65 pubmed publisher
    ..These findings demonstrate a new function for p110? as part of the membrane fission machinery required at the TGN for the selective trafficking and secretion of cytokines in macrophages. ..
  60. Zwaenepoel O, Tzenaki N, Vergetaki A, Makrigiannakis A, Vanhaesebroeck B, Papakonstanti E. Functional CSF-1 receptors are located at the nuclear envelope and activated via the p110? isoform of PI 3-kinase. FASEB J. 2012;26:691-706 pubmed publisher
    ..These findings may have important implications in cancer development. ..
  61. Thomas M, Smith A, Head D, Milne L, Nicholls A, Pearce W, et al. Airway inflammation: chemokine-induced neutrophilia and the class I phosphoinositide 3-kinases. Eur J Immunol. 2005;35:1283-91 pubmed
    ..No role for the delta isoform was demonstrated both in vitro and in vivo using PI3Kdelta kinase-dead knock-in mice...
  62. Acosta Y, Zafra M, Ojeda G, Bernardone I, Dianzani U, Portoles P, et al. Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible costimulator (CD278). Cell Mol Life Sci. 2011;68:3065-79 pubmed publisher
    ..Thus, p110? and p110? are essential to optimal T cell activation, but their abundance and activity differentially tune up distinct ICOS signaling pathways. ..
  63. Sun J, Mohlin S, Lundby A, Kazi J, Hellman U, Pahlman S, et al. The PI3-kinase isoform p110? is essential for cell transformation induced by the D816V mutant of c-Kit in a lipid-kinase-independent manner. Oncogene. 2014;33:5360-9 pubmed publisher
    ..This furthermore suggests that p110? could be a potential diagnostic factor and selective therapeutic target for c-Kit/D816V-expressing malignancies. ..
  64. Kim M, Kuehn H, Metcalfe D, Gilfillan A. Activation and function of the mTORC1 pathway in mast cells. J Immunol. 2008;180:4586-95 pubmed
    ..Specifically, the mTORC1 pathway may play a critical role in normal and dysregulated control of mast cell homeostasis. ..
  65. Kang B, Ha S, Ge X, Reza Hosseinkhani M, Bahaie N, Greenberg Y, et al. The p110? subunit of PI3K regulates bone marrow-derived eosinophil trafficking and airway eosinophilia in allergen-challenged mice. Am J Physiol Lung Cell Mol Physiol. 2012;302:L1179-91 pubmed publisher
  66. Liu S, Madiai F, Hackshaw K, Allen C, Carl J, Huschart E, et al. The large zinc finger protein ZAS3 is a critical modulator of osteoclastogenesis. PLoS ONE. 2011;6:e17161 pubmed publisher
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