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Gene Review

Pik3cb  -  phosphatidylinositol 3-kinase, catalytic,...

Mus musculus

Synonyms: 1110001J02Rik, AI447572, PI3-kinase subunit beta, PI3K-beta, PI3Kbeta, ...
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Disease relevance of Pik3cb


High impact information on Pik3cb

  • 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 [6].
  • Our work provides the first direct evidence that PI3K and its regulatory subunit have a role in glucose homeostasis in vivo [7].
  • In this study we have defined a key role for the Type Ia phosphoinositide 3-kinase (PI3K) p110beta isoform in regulating the formation and stability of integrin alpha(IIb)beta(3) adhesion bonds, necessary for shear activation of platelets [8].
  • Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice [9].
  • Intraperitoneal administration of TAT-Deltap85 caused time-dependent transduction into blood leukocytes, and inhibited activated phosphorylation of protein kinase B (PKB), a downstream target of PI3K, in lung tissues in mice receiving intranasal FMLP [10].

Chemical compound and disease context of Pik3cb


Biological context of Pik3cb


Anatomical context of Pik3cb

  • Here we report a specific recruitment of p110beta and p110delta (but not p110alpha) isoforms to the nascent phagosome during apoptotic cell phagocytosis by fibroblasts [14].
  • This work demonstrates that PI3K activity is critical for T cell development and depends on the combined function of p110gamma and p110delta [17].
  • This was partly correlated with an increase in p110alpha and p110beta protein levels both in some primary tumours and established cell lines, suggesting that PI3K overexpression is involved in enzymatic deregulation [2].
  • Using antibodies specific to p110alpha and to p110beta catalytic subunits, increase in PI3Kalpha and PI3Kbeta activities was detected in 15/19 human tumour biopsies relative to adjacent normal mucosa of human colon and bladder [2].
  • We compared the biochemical activity and transforming potential of mutant forms of p110alpha and p110beta in a human mammary epithelial cell system [15].

Associations of Pik3cb with chemical compounds

  • Class I phosphoinositide 3-kinase p110beta is required for apoptotic cell and Fcgamma receptor-mediated phagocytosis by macrophages [14].
  • Here we report that insulin causes an increase in wortmannin-sensitive PI 3-kinase activity and a gain in the enzyme's regulatory and catalytic subunits p85alpha and p110beta (but not p110alpha) in the intracellular compartments containing glucose transporters [18].
  • Analysis of tumor tissue from imatinib-treated mice showed diminished phosphatidylinositol 3-kinase (PI3-kinase) and mammalian target of rapamycin (mTOR) signaling suggesting that oncogenic Kit signaling critically contributes to the translational response in GIST [19].
  • Although both LY2 and wortmannin effectively blocked PI3K activity, wortmannin had little effect on FPR1 expression and did not modulate the decay of FPR1 mRNA [20].
  • Furthermore, available evidence indicates that GPCRs activate Akt by a pathway distinct from that utilized by growth factor receptors, as it involves the tyrosine phosphorylation-independent activation of PI3Kbeta by G protein betagamma dimers [21].

Regulatory relationships of Pik3cb

  • The effects of the increased p110 expression were further assessed by expressing epitope tagged p110beta and p110alpha in 3T3-L1 cells using adenovirus transduction systems, respectively [22].

Other interactions of Pik3cb

  • A specific function for phosphatidylinositol 3-kinase alpha (p85alpha-p110alpha) in cell survival and for phosphatidylinositol 3-kinase beta (p85alpha-p110beta) in de novo DNA synthesis of human colon carcinoma cells [2].
  • Indeed, both membrane redistribution and phosphorylation of Gab1 were reduced in the presence of PI3K inhibitors or dominant negative p110beta [23].
  • In addition, both PI 3- and PI 4-kinase activities of p110alpha and p110beta immunoprecipitates were similarly inhibited by either wortmannin or LY294002, specific inhibitors of p110 [24].
  • When p110alpha and p110beta were overexpressed in 3T3-L1 adipocytes, exposing cells to insulin induced each of the subunits to form complexes with p85alpha and tyrosine-phosphorylated IRS-1 with similar efficiency [22].

Analytical, diagnostic and therapeutic context of Pik3cb


  1. Phosphoinositide 3-kinase catalytic subunit deletion and regulatory subunit deletion have opposite effects on insulin sensitivity in mice. Brachmann, S.M., Ueki, K., Engelman, J.A., Kahn, R.C., Cantley, L.C. Mol. Cell. Biol. (2005) [Pubmed]
  2. A specific function for phosphatidylinositol 3-kinase alpha (p85alpha-p110alpha) in cell survival and for phosphatidylinositol 3-kinase beta (p85alpha-p110beta) in de novo DNA synthesis of human colon carcinoma cells. Bénistant, C., Chapuis, H., Roche, S. Oncogene (2000) [Pubmed]
  3. Type I phosphoinositide 3-kinases: potential antithrombotic targets? Jackson, S.F., Schoenwaelder, S.M. Cell. Mol. Life Sci. (2006) [Pubmed]
  4. Anaphylactic shock depends on PI3K and eNOS-derived NO. Cauwels, A., Janssen, B., Buys, E., Sips, P., Brouckaert, P. J. Clin. Invest. (2006) [Pubmed]
  5. The phosphoinositide 3-kinase/Akt pathway: a new target in human renal cell carcinoma therapy. Sourbier, C., Lindner, V., Lang, H., Agouni, A., Schordan, E., Danilin, S., Rothhut, S., Jacqmin, D., Helwig, J.J., Massfelder, T. Cancer Res. (2006) [Pubmed]
  6. 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]
  7. Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase. Terauchi, Y., Tsuji, Y., Satoh, S., Minoura, H., Murakami, K., Okuno, A., Inukai, K., Asano, T., Kaburagi, Y., Ueki, K., Nakajima, H., Hanafusa, T., Matsuzawa, Y., Sekihara, H., Yin, Y., Barrett, J.C., Oda, H., Ishikawa, T., Akanuma, Y., Komuro, I., Suzuki, M., Yamamura, K., Kodama, T., Suzuki, H., Yamamura, K., Kodama, T., Suzuki, H., Koyasu, S., Aizawa, S., Tobe, K., Fukui, Y., Yazaki, Y., Kadowaki, T. Nat. Genet. (1999) [Pubmed]
  8. 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]
  9. Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice. Fukao, T., Yamada, T., Tanabe, M., Terauchi, Y., Ota, T., Takayama, T., Asano, T., Takeuchi, T., Kadowaki, T., Hata Ji, J., Koyasu, S. Nat. Immunol. (2002) [Pubmed]
  10. Blockade of inflammation and airway hyperresponsiveness in immune-sensitized mice by dominant-negative phosphoinositide 3-kinase-TAT. Myou, S., Leff, A.R., Myo, S., Boetticher, E., Tong, J., Meliton, A.Y., Liu, J., Munoz, N.M., Zhu, X. J. Exp. Med. (2003) [Pubmed]
  11. 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]
  12. Significance of Akt phosphorylation on tumor growth and vascular endothelial growth factor expression in human gastric carcinoma. Kobayashi, I., Semba, S., Matsuda, Y., Kuroda, Y., Yokozaki, H. Pathobiology (2006) [Pubmed]
  13. Intracellular segregation of phosphatidylinositol-3,4,5-trisphosphate by insulin-dependent actin remodeling in L6 skeletal muscle cells. Patel, N., Rudich, A., Khayat, Z.A., Garg, R., Klip, A. Mol. Cell. Biol. (2003) [Pubmed]
  14. 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]
  15. The oncogenic properties of mutant p110alpha and p110beta phosphatidylinositol 3-kinases in human mammary epithelial cells. Zhao, J.J., Liu, Z., Wang, L., Shin, E., Loda, M.F., Roberts, T.M. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  16. 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]
  17. 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]
  18. Actin filaments participate in the relocalization of phosphatidylinositol3-kinase to glucose transporter-containing compartments and in the stimulation of glucose uptake in 3T3-L1 adipocytes. Wang, Q., Bilan, P.J., Tsakiridis, T., Hinek, A., Klip, A. Biochem. J. (1998) [Pubmed]
  19. Oncogenic Kit signaling and therapeutic intervention in a mouse model of gastrointestinal stromal tumor. Rossi, F., Ehlers, I., Agosti, V., Socci, N.D., Viale, A., Sommer, G., Yozgat, Y., Manova, K., Antonescu, C.R., Besmer, P. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  20. Signaling in lipopolysaccharide-induced stabilization of formyl Peptide receptor 1 mRNA in mouse peritoneal macrophages. Mandal, P., Hamilton, T. J. Immunol. (2007) [Pubmed]
  21. A novel role for phosphatidylinositol 3-kinase beta in signaling from G protein-coupled receptors to Akt. Murga, C., Fukuhara, S., Gutkind, J.S. J. Biol. Chem. (2000) [Pubmed]
  22. p110beta is up-regulated during differentiation of 3T3-L1 cells and contributes to the highly insulin-responsive glucose transport activity. Asano, T., Kanda, A., Katagiri, H., Nawano, M., Ogihara, T., Inukai, K., Anai, M., Fukushima, Y., Yazaki, Y., Kikuchi, M., Hooshmand-Rad, R., Heldin, C.H., Oka, Y., Funaki, M. J. Biol. Chem. (2000) [Pubmed]
  23. A function for phosphoinositide 3-kinase beta lipid products in coupling beta gamma to Ras activation in response to lysophosphatidic acid. Yart, A., Roche, S., Wetzker, R., Laffargue, M., Tonks, N., Mayeux, P., Chap, H., Raynal, P. J. Biol. Chem. (2002) [Pubmed]
  24. p85/p110-type phosphatidylinositol kinase phosphorylates not only the D-3, but also the D-4 position of the inositol ring. Funaki, M., Katagiri, H., Kanda, A., Anai, M., Nawano, M., Ogihara, T., Inukai, K., Fukushima, Y., Ono, H., Yazaki, Y., Kikuchi, M., Oka, Y., Asano, T. J. Biol. Chem. (1999) [Pubmed]
  25. Phosphatidylinositide 3-kinase localizes to cytoplasmic lipid bodies in human polymorphonuclear leukocytes and other myeloid-derived cells. Yu, W., Cassara, J., Weller, P.F. Blood (2000) [Pubmed]
  26. Region-specific mRNA expression of phosphatidylinositol 3-kinase regulatory isoforms in the central nervous system of C57BL/6J mice. Hörsch, D., Kahn, C.R. J. Comp. Neurol. (1999) [Pubmed]
  27. A function for phosphatidylinositol 3-kinase beta (p85alpha-p110beta) in fibroblasts during mitogenesis: requirement for insulin- and lysophosphatidic acid-mediated signal transduction. Roche, S., Downward, J., Raynal, P., Courtneidge, S.A. Mol. Cell. Biol. (1998) [Pubmed]
  28. An anti-inflammatory role for a phosphoinositide 3-kinase inhibitor LY294002 in a mouse asthma model. Duan, W., Aguinaldo Datiles, A.M., Leung, B.P., Vlahos, C.J., Wong, W.S. Int. Immunopharmacol. (2005) [Pubmed]
  29. PI 3-kinases: hidden potentials revealed. Vogt, P.K., Bader, A.G., Kang, S. Cell Cycle (2006) [Pubmed]
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