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Gene Review

PIK3CB  -  phosphatidylinositol-4,5-bisphosphate 3...

Homo sapiens

Synonyms: P110BETA, PI3-kinase subunit beta, PI3K, PI3K-beta, PI3KBETA, ...
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Disease relevance of PIK3CB


Psychiatry related information on PIK3CB


High impact information on PIK3CB

  • A PI3K has already been purified, cloned, and shown to be regulated by receptors that act via tyrosine kinase-dependent regulatory mechanisms [8].
  • Phosphoinositide 3 kinase (PI3K) is a key signaling enzyme implicated in receptor-stimulated mitogenesis, oxidative bursting in neutrophils, membrane ruffling, and glucose uptake [8].
  • 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 [8].
  • 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 [9].
  • Isoform-selective PI3K p110beta inhibitors have been developed which prevent formation of stable integrin alpha(IIb)beta(3) adhesion contacts, leading to defective platelet thrombus formation [9].

Chemical compound and disease context of PIK3CB


Biological context of PIK3CB


Anatomical context of PIK3CB

  • Northern (RNA) analysis demonstrated expression of human PI 3-kinase in all tissues and cell lines tested [15].
  • In contrast, SPP and DHSPP recruit PI3Kbeta isozyme into NK cell membranes, suggesting that although this isoform is not involved in chemotaxis, it is activated by these phospholipids [16].
  • Such enzymatic properties were also observed with a recombinant p110 beta/p85 alpha expressed in COS-7 cells [17].
  • Activation of PI 3-kinase at the plasma membrane is accompanied by the recruitment of Rab5, PI 4-, and PI 5-phosphatases to the cell cortex [18].
  • The inhibition of myotube formation and the reduced expression of muscle-specific proteins caused by the PI 3-kinase inhibitor LY294002 are completely reversed by constitutively active forms of Akt [19].

Associations of PIK3CB with chemical compounds

  • A glutathione S-transferase fusion protein containing the N-terminal 171 amino-acids of p110 beta bound to free p85 in cell lysates [20].
  • Treatment of MM cells with the PI3K inhibitor LY294002 in combination with cisplatin had greater efficacy in inhibiting cell proliferation and inducing apoptosis than either agent alone [21].
  • Previously, nucleophosmin-ALK has been shown to activate phosphatidylinositol 3-kinase (PI3K) and its downstream effector, the serine/threonine kinase AKT [22].
  • Increased basal phosphorylation of Ser307 IRS-1 in the obese and type 2 diabetic subjects corresponds with decrease in insulin-stimulated IRS-1 tyrosine phosphorylation, PI 3-kinase activity, and insulin-induced activation of Akt and, more prominently, PKC-zeta/lambda [23].
  • Caffeine and theophylline also inhibit the intrinsic protein kinase activity of the class IA PI3Ks and DNA-dependent protein kinase, although with a much lower potency than that for the lipid kinase (IC(50) approximately 10 mm for p110 alpha, 3 mm for p110 beta, and 10 mm for DNA-dependent protein kinase) [24].

Physical interactions of PIK3CB


Enzymatic interactions of PIK3CB

  • However, p110 beta is far less efficient at phosphorylating p85 alpha Ser608, identifying a potential difference in the mechanisms by which these two isoforms are regulated [26].

Regulatory relationships of PIK3CB

  • HGF was found to significantly activate Akt phosphorylation while pre-treatment with PI3K specific inhibitor wortmannin further enhanced ActD-induced apoptotic effect, and also significantly prevented HGF's protection against ActD-induced apoptosis [27].

Other interactions of PIK3CB

  • Blocking antibody to PI3Kgamma inhibits the chemotaxis induced by the three ligands, whereas anti-PI3Kbeta was without effect [16].
  • In the present study we characterize the subcellular distribution of the novel class II PI3K isozyme PI3K-C2alpha in several mammalian cell types [28].
  • Since phosphatidylinositol-3 kinase (PI3K)/Akt pathway is essential for cell survival, the present study has examined whether the preventive effect of hepatocyte growth factor (HGF) on ActD-induced apoptotic cell death in a human hepatocyte-derived cell line (HL7702) is associated with PI3K/Akt activation [27].
  • Consistent with these data, forskolin, isoproterenol, a PI3K inhibitor, or a Rho kinase inhibitor, but not a PKC inhibitor, abolished KCl-induced diphosphorylation of MLC [29].

Analytical, diagnostic and therapeutic context of PIK3CB


  1. Mutation analysis of PIK3CA and PIK3CB in esophageal cancer and Barrett's esophagus. Phillips, W.A., Russell, S.E., Ciavarella, M.L., Choong, D.Y., Montgomery, K.G., Smith, K., Pearson, R.B., Thomas, R.J., Campbell, I.G. Int. J. Cancer (2006) [Pubmed]
  2. Downregulation of PIK3CB by siRNA suppresses malignant glioma cell growth in vitro and in vivo. Pu, P., Kang, C., Zhang, Z., Liu, X., Jiang, H. Technol. Cancer Res. Treat. (2006) [Pubmed]
  3. Continuous signaling via PI3K isoforms beta and {gamma} is required for platelet ADP receptor function in dynamic thrombus stabilization. Cosemans, J.M., Munnix, I.C., Wetzker, R., Heller, R., Jackson, S.P., Heemskerk, J.W. Blood (2006) [Pubmed]
  4. Over-expression of the p110beta but not p110alpha isoform of PI 3-kinase inhibits motility in breast cancer cells. Yip, S.C., El-Sibai, M., Hill, K.M., Wu, H., Fu, Z., Condeelis, J.S., Backer, J.M. Cell Motil. Cytoskeleton (2004) [Pubmed]
  5. Activation of protein kinase B/Akt in the periphery contributes to pain behavior induced by capsaicin in rats. Sun, R., Yan, J., Willis, W.D. Neuroscience (2007) [Pubmed]
  6. 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]
  7. 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]
  8. 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]
  9. 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]
  10. 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]
  11. PI3K signalling during influenza A virus infections. Hale, B.G., Randall, R.E. Biochem. Soc. Trans. (2007) [Pubmed]
  12. Neuroprotection of selenite against ischemic brain injury through negatively regulating early activation of ASK1/JNK cascade via activation of PI3K/AKT pathway. Wang, Q., Zhang, Q.G., Wu, D.N., Yin, X.H., Zhang, G.Y. Acta Pharmacol. Sin. (2007) [Pubmed]
  13. 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]
  14. 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]
  15. Cloning of a novel, ubiquitously expressed human phosphatidylinositol 3-kinase and identification of its binding site on p85. Hu, P., Mondino, A., Skolnik, E.Y., Schlessinger, J. Mol. Cell. Biol. (1993) [Pubmed]
  16. Sphingosine 1 phosphate induces the chemotaxis of human natural killer cells. Role for heterotrimeric G proteins and phosphoinositide 3 kinases. Kveberg, L., Bryceson, Y., Inngjerdingen, M., Rolstad, B., Maghazachi, A.A. Eur. J. Immunol. (2002) [Pubmed]
  17. Synergistic activation of a family of phosphoinositide 3-kinase via G-protein coupled and tyrosine kinase-related receptors. Katada, T., Kurosu, H., Okada, T., Suzuki, T., Tsujimoto, N., Takasuga, S., Kontani, K., Hazeki, O., Ui, M. Chem. Phys. Lipids (1999) [Pubmed]
  18. An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway. Shin, H.W., Hayashi, M., Christoforidis, S., Lacas-Gervais, S., Hoepfner, S., Wenk, M.R., Modregger, J., Uttenweiler-Joseph, S., Wilm, M., Nystuen, A., Frankel, W.N., Solimena, M., De Camilli, P., Zerial, M. J. Cell Biol. (2005) [Pubmed]
  19. Myogenic signaling of phosphatidylinositol 3-kinase requires the serine-threonine kinase Akt/protein kinase B. Jiang, B.H., Aoki, M., Zheng, J.Z., Li, J., Vogt, P.K. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  20. Direct association of p110 beta phosphatidylinositol 3-kinase with p85 is mediated by an N-terminal fragment of p110 beta. Hu, P., Schlessinger, J. Mol. Cell. Biol. (1994) [Pubmed]
  21. Human and mouse mesotheliomas exhibit elevated AKT/PKB activity, which can be targeted pharmacologically to inhibit tumor cell growth. Altomare, D.A., You, H., Xiao, G.H., Ramos-Nino, M.E., Skele, K.L., De Rienzo, A., Jhanwar, S.C., Mossman, B.T., Kane, A.B., Testa, J.R. Oncogene (2005) [Pubmed]
  22. Activation of mammalian target of rapamycin signaling pathway contributes to tumor cell survival in anaplastic lymphoma kinase-positive anaplastic large cell lymphoma. Vega, F., Medeiros, L.J., Leventaki, V., Atwell, C., Cho-Vega, J.H., Tian, L., Claret, F.X., Rassidakis, G.Z. Cancer Res. (2006) [Pubmed]
  23. Increased p85/55/50 expression and decreased phosphotidylinositol 3-kinase activity in insulin-resistant human skeletal muscle. Bandyopadhyay, G.K., Yu, J.G., Ofrecio, J., Olefsky, J.M. Diabetes (2005) [Pubmed]
  24. Direct effects of caffeine and theophylline on p110 delta and other phosphoinositide 3-kinases. Differential effects on lipid kinase and protein kinase activities. Foukas, L.C., Daniele, N., Ktori, C., Anderson, K.E., Jensen, J., Shepherd, P.R. J. Biol. Chem. (2002) [Pubmed]
  25. Detection of the p110 beta subunit of phosphatidylinositol 3-kinase complexed with neutral endopeptidase. Shen, R., Milowsky, M.I., Ozaki, N., Navarro, D., Sumitomo, M., Xu, Y., Nanus, D.M. Anticancer Res. (2002) [Pubmed]
  26. Regulation of phosphoinositide 3-kinase by its intrinsic serine kinase activity in vivo. Foukas, L.C., Beeton, C.A., Jensen, J., Phillips, W.A., Shepherd, P.R. Mol. Cell. Biol. (2004) [Pubmed]
  27. Anti-apoptotic effect of hepatocyte growth factor from actinomycin D in hepatocyte-derived HL7702 cells is associated with activation of PI3K/Akt signaling. Li, W., Cai, S., Cai, L., Li, X. Toxicol. Lett. (2006) [Pubmed]
  28. The class II phosphoinositide 3-kinase PI3K-C2alpha is concentrated in the trans-Golgi network and present in clathrin-coated vesicles. Domin, J., Gaidarov, I., Smith, M.E., Keen, J.H., Waterfield, M.D. J. Biol. Chem. (2000) [Pubmed]
  29. Ca2+-Independent, Inhibitory Effects of Cyclic Adenosine 5'-Monophosphate on Ca2+ Regulation of Phosphoinositide 3-Kinase C2{alpha}, Rho, and Myosin Phosphatase in Vascular Smooth Muscle. Azam, M.A., Yoshioka, K., Ohkura, S., Takuwa, N., Sugimoto, N., Sato, K., Takuwa, Y. J. Pharmacol. Exp. Ther. (2007) [Pubmed]
  30. 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]
  31. Photoperiodic regulation of insulin receptor mRNA and intracellular insulin signaling in the arcuate nucleus of the Siberian hamster, Phodopus sungorus. Tups, A., Helwig, M., Stöhr, S., Barrett, P., Mercer, J.G., Klingenspor, M. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2006) [Pubmed]
  32. PWT-458, a novel pegylated-17-hydroxywortmannin, inhibits phosphatidylinositol 3-kinase signaling and suppresses growth of solid tumors. Yu, K., Lucas, J., Zhu, T., Zask, A., Gaydos, C., Toral-Barza, L., Gu, J., Li, F., Chaudhary, I., Cai, P., Lotvin, J., Petersen, R., Ruppen, M., Fawzi, M., Ayral-Kaloustian, S., Skotnicki, J., Mansour, T., Frost, P., Gibbons, J. Cancer Biol. Ther. (2005) [Pubmed]
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