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Gene Review

PIK3CD  -  phosphatidylinositol-4,5-bisphosphate 3...

Homo sapiens

Synonyms: APDS, IMD14, P110DELTA, PI3-kinase subunit delta, PI3K, ...
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Disease relevance of PIK3CD


Psychiatry related information on PIK3CD


High impact information on PIK3CD

  • A PI3K has already been purified, cloned, and shown to be regulated by receptors that act via tyrosine kinase-dependent regulatory mechanisms [9].
  • Phosphoinositide 3 kinase (PI3K) is a key signaling enzyme implicated in receptor-stimulated mitogenesis, oxidative bursting in neutrophils, membrane ruffling, and glucose uptake [9].
  • We report that an immunologically, pharmacologically, and chromatographically distinct form of PI3K activity present in neutrophils and U937 cells is specifically activated by G protein beta gamma subunits [9].
  • The phosphoinositide 3-kinase (PI3K) family of enzymes is recruited upon growth factor receptor activation and produces 3' phosphoinositide lipids [10].
  • The lipid products of PI3K act as second messengers by binding to and activating diverse cellular target proteins [10].

Chemical compound and disease context of PIK3CD


Biological context of PIK3CD

  • However, p110delta that is recruited to activated receptors (such as CD28 in T cells) shows a time-dependent increase in Ser1039 phosphorylation and a concomitant decrease in associated lipid kinase activity [16].
  • Tracking analysis of IC87114-treated neutrophils indicated that PI3K delta activity was required for the directional component of chemotaxis, but not for random movement [17].
  • PTEN phosphatase, a product of PTEN tumor suppressor gene, exists in cells in phosphorylated and unphosphorylated form and has a central role in regulation of PI3K/Akt signalling which is involved in non-genomic action of estradiol [18].
  • Recent evidence indicates that phosphatidylinositol 3-kinase (PI3K) is a central regulator of mitosis, apoptosis and oncogenesis [19].
  • Thus, we delineate a novel SRF-dependent mitogenic cascade that is critical for PI3K- and growth factor-mediated cell cycle progression [19].

Anatomical context of PIK3CD

  • Inhibition of PI3K delta, however, did not block F-actin synthesis or neutrophil adhesion [17].
  • The results demonstrate that T. cruzi, through its TS, triggers the survival of host Schwann cells via the PI3K/Akt pathway, suggesting a role for PI3K/Akt in the pathogenesis of Chagas' disease [20].
  • Surprisingly, genetic deletion of the p110delta and p110gamma catalytic subunits resulted in a dramatic reduction in thymus size, cellularity, and lack of corticomedullary differentiation [21].
  • 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 [22].
  • We show that treatment of macrophages with ATP results in production of reactive oxygen species (ROS), which stimulate the phosphatidylinositol 3-kinase (PI3K) pathway and subsequent Akt and ERK1/2 activation [23].

Associations of PIK3CD with chemical compounds


Regulatory relationships of PIK3CD

  • In contrast, inactivation of p110delta significantly impaired the ability of B cells to activate T cells in a BCR-mediated Ag uptake and presentation model [22].

Other interactions of PIK3CD

  • PI3Ks are critical signaling enzymes controlling many cellular processes, with the p110delta isoform playing a critical role in BCR signaling [22].

Analytical, diagnostic and therapeutic context of PIK3CD

  • Consistent with previous data, antibodies against p110delta and p110beta blocked FcepsilonR1-mediated degranulation in response to FcepsilonRI ligation [25].
  • Recently, it has been shown that Sonic Hedgehog-induced formation of medulloblastoma in an animal model is significantly enhanced by activation of the phosphatidylinositol 3'-kinase (PI3K) signaling pathway [26].
  • As assessed by Western blotting, protein levels of the serum-, and glucocorticoid-induced kinase (Sgk1) were directly and proportionally related to the current induced by either or both IGF-1 and aldosterone, effects also blocked by the PI3-K inhibitor LY294002 [27].
  • The purification yields were high using the optimized ratio of p85/p110 vector and small culture volumes, with 24mg/L cell culture media for p85alpha/p110alpha, 17.5mg/L for p85alpha/p110delta, and 3.5mg/L for p85alpha/p110beta [28].
  • This class of PI 3-kinase was identified exclusively by PCR and homology cloning approaches and not on the basis of cellular function [29].


  1. Genetic alterations of phosphoinositide 3-kinase subunit genes in human glioblastomas. Mizoguchi, M., Nutt, C.L., Mohapatra, G., Louis, D.N. Brain Pathol. (2004) [Pubmed]
  2. Oncogenic transformation induced by the p110beta, -gamma, and -delta isoforms of class I phosphoinositide 3-kinase. Kang, S., Denley, A., Vanhaesebroeck, B., Vogt, P.K. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. Essential role for the p110delta isoform in phosphoinositide 3-kinase activation and cell proliferation in acute myeloid leukemia. Sujobert, P., Bardet, V., Cornillet-Lefebvre, P., Hayflick, J.S., Prie, N., Verdier, F., Vanhaesebroeck, B., Muller, O., Pesce, F., Ifrah, N., Hunault-Berger, M., Berthou, C., Villemagne, B., Jourdan, E., Audhuy, B., Solary, E., Witz, B., Harousseau, J.L., Himberlin, C., Lamy, T., Lioure, B., Cahn, J.Y., Dreyfus, F., Mayeux, P., Lacombe, C., Bouscary, D. Blood (2005) [Pubmed]
  4. Identification and chromosome assignment of a human gene encoding a novel phosphatidylinositol-3 kinase. Seki, N., Nimura, Y., Ohira, M., Saito, T., Ichimiya, S., Nomura, N., Nakagawara, A. DNA Res. (1997) [Pubmed]
  5. A role for adrenomedullin as a pain-related peptide in the rat. Ma, W., Chabot, J.G., Quirion, R. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  6. Tumor suppressor PTEN affects tau phosphorylation: deficiency in the phosphatase activity of PTEN increases aggregation of an FTDP-17 mutant Tau. Zhang, X., Zhang, Y.W., Liu, S., Bulloj, A., Tong, G.G., Zhang, Z., Liao, F.F., Xu, H. Molecular neurodegeneration [electronic resource]. (2006) [Pubmed]
  7. Control of neurite outgrowth and growth cone motility by phosphatidylinositol-3-kinase. Tornieri, K., Welshhans, K., Geddis, M.S., Rehder, V. Cell Motil. Cytoskeleton (2006) [Pubmed]
  8. Phosphatidylinositol 3-kinase in the G protein-coupled receptor-induced chemokinesis and chemotaxis of MDA-MB-468 breast carcinoma cells: a comparison with leukocytes. Bastian, P., Posch, B., Lang, K., Niggemann, B., Zaenker, K.S., Hatt, H., Entschladen, F. Mol. Cancer Res. (2006) [Pubmed]
  9. A novel phosphoinositide 3 kinase activity in myeloid-derived cells is activated by G protein beta gamma subunits. Stephens, L., Smrcka, A., Cooke, F.T., Jackson, T.R., Sternweis, P.C., Hawkins, P.T. Cell (1994) [Pubmed]
  10. Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer. Katso, R., Okkenhaug, K., Ahmadi, K., White, S., Timms, J., Waterfield, M.D. Annu. Rev. Cell Dev. Biol. (2001) [Pubmed]
  11. Inhibition of EGFR/PI3K/AKT cell survival pathway promotes TSA's effect on cell death and migration in human ovarian cancer cells. Zhou, C., Qiu, L., Sun, Y., Healey, S., Wanebo, H., Kouttab, N., Di, W., Yan, B., Wan, Y. Int. J. Oncol. (2006) [Pubmed]
  12. Roles of the RAF/MEK/ERK and PI3K/PTEN/AKT pathways in malignant transformation and drug resistance. McCubrey, J.A., Steelman, L.S., Abrams, S.L., Lee, J.T., Chang, F., Bertrand, F.E., Navolanic, P.M., Terrian, D.M., Franklin, R.A., D'Assoro, A.B., Salisbury, J.L., Mazzarino, M.C., Stivala, F., Libra, M. Adv. Enzyme Regul. (2006) [Pubmed]
  13. Targeted molecular therapy of the PI3K pathway: therapeutic significance of PI3K subunit targeting in colorectal carcinoma. Rychahou, P.G., Jackson, L.N., Silva, S.R., Rajaraman, S., Evers, B.M. Ann. Surg. (2006) [Pubmed]
  14. Reversal of Taxol resistance in hepatoma by cyclosporin A: involvement of the PI-3 kinase-AKT 1 pathway. Lin, H.L., Lui, W.Y., Liu, T.Y., Chi, C.W. Br. J. Cancer (2003) [Pubmed]
  15. ECM overrides DNA damage-induced cell cycle arrest and apoptosis in small-cell lung cancer cells through beta1 integrin-dependent activation of PI3-kinase. Hodkinson, P.S., Elliott, T., Wong, W.S., Rintoul, R.C., Mackinnon, A.C., Haslett, C., Sethi, T. Cell Death Differ. (2006) [Pubmed]
  16. Autophosphorylation of p110delta phosphoinositide 3-kinase: a new paradigm for the regulation of lipid kinases in vitro and in vivo. Vanhaesebroeck, B., Higashi, K., Raven, C., Welham, M., Anderson, S., Brennan, P., Ward, S.G., Waterfield, M.D. EMBO J. (1999) [Pubmed]
  17. Essential role of phosphoinositide 3-kinase delta in neutrophil directional movement. Sadhu, C., Masinovsky, B., Dick, K., Sowell, C.G., Staunton, D.E. J. Immunol. (2003) [Pubmed]
  18. Phosphorylation of PTEN (phosphatase and tensin homologue deleted on chromosome ten) protein is enhanced in human fibromyomatous uteri. Kovács, K.A., Lengyel, F., Vértes, Z., Környei, J.L., Gocze, P.M., Sumegi, B., Szabó, I., Vértes, M. J. Steroid Biochem. Mol. Biol. (2007) [Pubmed]
  19. SRF-dependent gene expression is required for PI3-kinase-regulated cell proliferation. Poser, S., Impey, S., Trinh, K., Xia, Z., Storm, D.R. EMBO J. (2000) [Pubmed]
  20. Trypanosoma cruzi trans-sialidase: a potent and specific survival factor for human Schwann cells by means of phosphatidylinositol 3-kinase/Akt signaling. Chuenkova, M.V., Furnari, F.B., Cavenee, W.K., Pereira, M.A. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  21. Essential role of PI3Kdelta and PI3Kgamma in thymocyte survival. Swat, W., Montgrain, V., Doggett, T.A., Douangpanya, J., Puri, K., Vermi, W., Diacovo, T.G. Blood (2006) [Pubmed]
  22. Requirement for Phosphoinositide 3-Kinase p110{delta} Signaling in B Cell Antigen Receptor-Mediated Antigen Presentation. Al-Alwan, M.M., Okkenhaug, K., Vanhaesebroeck, B., Hayflick, J.S., Marshall, A.J. J. Immunol. (2007) [Pubmed]
  23. ATP Activates a Reactive Oxygen Species-dependent Oxidative Stress Response and Secretion of Proinflammatory Cytokines in Macrophages. Cruz, C.M., Rinna, A., Forman, H.J., Ventura, A.L., Persechini, P.M., Ojcius, D.M. J. Biol. Chem. (2007) [Pubmed]
  24. CCL5 evokes calcium signals in microglia through a kinase-, phosphoinositide-, and nucleotide-dependent mechanism. Shideman, C.R., Hu, S., Peterson, P.K., Thayer, S.A. J. Neurosci. Res. (2006) [Pubmed]
  25. Distinct phosphoinositide 3-kinases mediate mast cell degranulation in response to G-protein-coupled versus FcepsilonRI receptors. Windmiller, D.A., Backer, J.M. J. Biol. Chem. (2003) [Pubmed]
  26. Phosphatidylinositol 3'-kinase/AKT signaling is activated in medulloblastoma cell proliferation and is associated with reduced expression of PTEN. Hartmann, W., Digon-Söntgerath, B., Koch, A., Waha, A., Endl, E., Dani, I., Denkhaus, D., Goodyer, C.G., Sörensen, N., Wiestler, O.D., Pietsch, T. Clin. Cancer Res. (2006) [Pubmed]
  27. IGF-1 vs insulin: Respective roles in modulating sodium transport via the PI-3 kinase/Sgk1 pathway in a cortical collecting duct cell line. Gonzalez-Rodriguez, E., Gaeggeler, H.P., Rossier, B.C. Kidney Int. (2007) [Pubmed]
  28. Cloning, expression, purification, and characterization of the human Class Ia phosphoinositide 3-kinase isoforms. Meier, T.I., Cook, J.A., Thomas, J.E., Radding, J.A., Horn, C., Lingaraj, T., Smith, M.C. Protein Expr. Purif. (2004) [Pubmed]
  29. Are class II phosphoinositide 3-kinases potential targets for anticancer therapies? Traer, C.J., Foster, F.M., Abraham, S.M., Fry, M.J. Bulletin du cancer. (2006) [Pubmed]
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