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Gene Review

Pik3cd  -  phosphatidylinositol 3-kinase catalytic...

Mus musculus

Synonyms: 2410099E07Rik, 2610208K16Rik, AW545373, PI3-kinase subunit delta, PI3K-delta, ...
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Disease relevance of Pik3cd


Psychiatry related information on Pik3cd

  • AVP was also effective in reducing the maximal electroshock (MES) induced convulsive time and this protective effect was blocked by PI-3 kinase inhibitors [6].

High impact information on Pik3cd

  • We find that p110alpha is the primary insulin-responsive PI3-K in cultured cells, whereas p110beta is dispensable but sets a phenotypic threshold for p110alpha activity [7].
  • These results suggested that PI3-kinase binds two phosphotyrosine residues, each located in a 5 aa motif with an essential methionine at the fourth position C-terminal to the tyrosine [8].
  • Therefore, GAP and PI3-kinase interact with the receptor by binding to different phosphotyrosine-containing sequence motifs [8].
  • Mutation of the binding site for GAP prevented the receptor from associating with or phosphorylating GAP, but had no effect on PI3-kinase binding and little effect on DNA synthesis [8].
  • Point mutations at these sites caused a selective elimination of PI3-kinase binding and loss of PDGF-stimulated DNA synthesis [8].

Chemical compound and disease context of Pik3cd


Biological context of Pik3cd

  • In addition, the p110delta catalytic domain contains unique potential protein-protein interaction modules such as a Pro-rich region and a basic-region leucine-zipper (bZIP)-like domain [14].
  • Like p110alpha and p110beta, other class I PI3Ks, p110delta displays a broad phosphoinositide lipid substrate specificity and interacts with SH2/SH3 domain-containing p85 adaptor proteins and with GTP-bound Ras [14].
  • Macrophages from mice expressing a catalytically inactive form of p110delta showed no defect in the phagocytosis of apoptotic cells and IgG-opsonized particles, confirming the lack of a major role for p110delta in this process [15].
  • Thus, p110delta plays a critical role in B cell homeostasis and function [16].
  • Here, in vitro phospholipase assays establish that the phosphatidylinositol 3-kinase (PI 3-kinase) lipid product, phosphatidylinositol 3,4,5-triphosphate, further stimulates phospholipase Cgamma2 that has been activated by conformational changes associated with tyrosine phosphorylation or low pH [17].

Anatomical context of Pik3cd


Associations of Pik3cd with chemical compounds

  • 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 [20].
  • Role of the p110delta PI 3-kinase in integrin and ITAM receptor signalling in platelets [20].
  • This indicates a requirement for Ins(1,4,5)P3 to initiate and sustain Ca2+ responses even when PI 3-kinase is fully active [17].
  • Antigen-induced cell ruffling, a calcium-independent event, is blocked by injection of p110beta and p110delta antibodies, but not by injection of 5-phosphatase I, heparin, or anti-p110alpha antibodies [17].
  • p110beta and p110delta phosphatidylinositol 3-kinases up-regulate Fc(epsilon)RI-activated Ca2+ influx by enhancing inositol 1,4,5-trisphosphate production [17].

Other interactions of Pik3cd


Analytical, diagnostic and therapeutic context of Pik3cd


  1. Phosphatidylinositol 3-kinase association with the osteoclast cytoskeleton, and its involvement in osteoclast attachment and spreading. Lakkakorpi, P.T., Wesolowski, G., Zimolo, Z., Rodan, G.A., Rodan, S.B. Exp. Cell Res. (1997) [Pubmed]
  2. Airway inflammation: chemokine-induced neutrophilia and the class I phosphoinositide 3-kinases. Thomas, M.J., Smith, A., Head, D.H., Milne, L., Nicholls, A., Pearce, W., Vanhaesebroeck, B., Wymann, M.P., Hirsch, E., Trifilieff, A., Walker, C., Finan, P., Westwick, J. Eur. J. Immunol. (2005) [Pubmed]
  3. Adenovirus-induced maturation of dendritic cells through a PI3 kinase-mediated TNF-alpha induction pathway. Philpott, N.J., Nociari, M., Elkon, K.B., Falck-Pedersen, E. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. 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. Bilancio, A., Okkenhaug, K., Camps, M., Emery, J.L., Ruckle, T., Rommel, C., Vanhaesebroeck, B. Blood (2006) [Pubmed]
  5. Hedgehog and PI-3 kinase signaling converge on Nmyc1 to promote cell cycle progression in cerebellar neuronal precursors. Kenney, A.M., Widlund, H.R., Rowitch, D.H. Development (2004) [Pubmed]
  6. Vasopressin mediates neuroprotection in mice by stimulation of V1 vasopressin receptors: influence of PI-3 kinase and gap junction inhibitors. Tyagi, M.G., Parthiban, K.V. Indian J. Exp. Biol. (2003) [Pubmed]
  7. A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Knight, Z.A., Gonzalez, B., Feldman, M.E., Zunder, E.R., Goldenberg, D.D., Williams, O., Loewith, R., Stokoe, D., Balla, A., Toth, B., Balla, T., Weiss, W.A., Williams, R.L., Shokat, K.M. Cell (2006) [Pubmed]
  8. Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathways. Fantl, W.J., Escobedo, J.A., Martin, G.A., Turck, C.W., del Rosario, M., McCormick, F., Williams, L.T. Cell (1992) [Pubmed]
  9. Regulation of breast cancer cell chemotaxis by the phosphoinositide 3-kinase p110delta. Sawyer, C., Sturge, J., Bennett, D.C., O'Hare, M.J., Allen, W.E., Bain, J., Jones, G.E., Vanhaesebroeck, B. Cancer Res. (2003) [Pubmed]
  10. Phosphoinositide 3-kinase in nitric oxide synthesis in macrophage: critical dimerization of inducible nitric-oxide synthase. Sakai, K., Suzuki, H., Oda, H., Akaike, T., Azuma, Y., Murakami, T., Sugi, K., Ito, T., Ichinose, H., Koyasu, S., Shirai, M. J. Biol. Chem. (2006) [Pubmed]
  11. Tyrosine phosphorylation of p120cbl in BCR/abl transformed hematopoietic cells mediates enhanced association with phosphatidylinositol 3-kinase. Jain, S.K., Langdon, W.Y., Varticovski, L. Oncogene (1997) [Pubmed]
  12. The acute and chronic stimulatory effects of endothelin-1 on glucose transport are mediated by distinct pathways in 3T3-L1 adipocytes. Ishibashi, K., Imamura, T., Sharma, P.M., Ugi, S., Olefsky, J.M. Endocrinology (2000) [Pubmed]
  13. PI 3-kinase p110beta: a new target for antithrombotic therapy. Jackson, S.P., Schoenwaelder, S.M., Goncalves, I., Nesbitt, W.S., Yap, C.L., Wright, C.E., Kenche, V., Anderson, K.E., Dopheide, S.M., Yuan, Y., Sturgeon, S.A., Prabaharan, H., Thompson, P.E., Smith, G.D., Shepherd, P.R., Daniele, N., Kulkarni, S., Abbott, B., Saylik, D., Jones, C., Lu, L., Giuliano, S., Hughan, S.C., Angus, J.A., Robertson, A.D., Salem, H.H. Nat. Med. (2005) [Pubmed]
  14. P110delta, a novel phosphoinositide 3-kinase in leukocytes. Vanhaesebroeck, B., Welham, M.J., Kotani, K., Stein, R., Warne, P.H., Zvelebil, M.J., Higashi, K., Volinia, S., Downward, J., Waterfield, M.D. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  15. Class I phosphoinositide 3-kinase p110beta is required for apoptotic cell and Fcgamma receptor-mediated phagocytosis by macrophages. Leverrier, Y., Okkenhaug, K., Sawyer, C., Bilancio, A., Vanhaesebroeck, B., Ridley, A.J. J. Biol. Chem. (2003) [Pubmed]
  16. A crucial role for the p110delta subunit of phosphatidylinositol 3-kinase in B cell development and activation. Clayton, E., Bardi, G., Bell, S.E., Chantry, D., Downes, C.P., Gray, A., Humphries, L.A., Rawlings, D., Reynolds, H., Vigorito, E., Turner, M. J. Exp. Med. (2002) [Pubmed]
  17. p110beta and p110delta phosphatidylinositol 3-kinases up-regulate Fc(epsilon)RI-activated Ca2+ influx by enhancing inositol 1,4,5-trisphosphate production. Smith, A.J., Surviladze, Z., Gaudet, E.A., Backer, J.M., Mitchell, C.A., Wilson, B.S. J. Biol. Chem. (2001) [Pubmed]
  18. The role of endothelial PI3Kgamma activity in neutrophil trafficking. Puri, K.D., Doggett, T.A., Huang, C.Y., Douangpanya, J., Hayflick, J.S., Turner, M., Penninger, J., Diacovo, T.G. Blood (2005) [Pubmed]
  19. Cutting edge: T cell development requires the combined activities of the p110gamma and p110delta catalytic isoforms of phosphatidylinositol 3-kinase. Webb, L.M., Vigorito, E., Wymann, M.P., Hirsch, E., Turner, M. J. Immunol. (2005) [Pubmed]
  20. Role of the p110delta PI 3-kinase in integrin and ITAM receptor signalling in platelets. Senis, Y.A., Atkinson, B.T., Pearce, A.C., Wonerow, P., Auger, J.M., Okkenhaug, K., Pearce, W., Vigorito, E., Vanhaesebroeck, B., Turner, M., Watson, S.P. Platelets (2005) [Pubmed]
  21. The p110delta subunit of phosphoinositide 3-kinase is required for the lipopolysaccharide response of mouse B cells. Hebeis, B.J., Vigorito, E., Turner, M. Biochem. Soc. Trans. (2004) [Pubmed]
  22. Cutting edge: differential roles for phosphoinositide 3-kinases, p110gamma and p110delta, in lymphocyte chemotaxis and homing. Reif, K., Okkenhaug, K., Sasaki, T., Penninger, J.M., Vanhaesebroeck, B., Cyster, J.G. J. Immunol. (2004) [Pubmed]
  23. Mechanisms and implications of phosphoinositide 3-kinase delta in promoting neutrophil trafficking into inflamed tissue. Puri, K.D., Doggett, T.A., Douangpanya, J., Hou, Y., Tino, W.T., Wilson, T., Graf, T., Clayton, E., Turner, M., Hayflick, J.S., Diacovo, T.G. Blood (2004) [Pubmed]
  24. A specific antagonist of the p110delta catalytic component of phosphatidylinositol 3'-kinase, IC486068, enhances radiation-induced tumor vascular destruction. Geng, L., Tan, J., Himmelfarb, E., Schueneman, A., Niermann, K., Brousal, J., Fu, A., Cuneo, K., Kesicki, E.A., Treiberg, J., Hayflick, J.S., Hallahan, D.E. Cancer Res. (2004) [Pubmed]
  25. Impaired B and T cell antigen receptor signaling in p110delta PI 3-kinase mutant mice. Okkenhaug, K., Bilancio, A., Farjot, G., Priddle, H., Sancho, S., Peskett, E., Pearce, W., Meek, S.E., Salpekar, A., Waterfield, M.D., Smith, A.J., Vanhaesebroeck, B. Science (2002) [Pubmed]
  26. Selective role of PI3K delta in neutrophil inflammatory responses. Sadhu, C., Dick, K., Tino, W.T., Staunton, D.E. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  27. Regulation of phosphatidylinositol 3-kinase by polyisoprenyl phosphates in neutrophil-mediated tissue injury. Bonnans, C., Fukunaga, K., Keledjian, R., Petasis, N.A., Levy, B.D. J. Exp. Med. (2006) [Pubmed]
  28. Mouse phosphoinositide 3-kinase p110alpha gene: cloning, structural organization, and localization to chromosome 3 band B. Aksoy, I.A., Ramsey, M.J., Fruman, D.A., Aksoy, S., Cantley, L.C., Tucker, J.D., Roberts, T.M. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
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