The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Pik3ca  -  phosphatidylinositol 3-kinase, catalytic,...

Mus musculus

Synonyms: 6330412C24Rik, PI3-kinase subunit alpha, PI3K-alpha, PI3Kalpha, Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Pik3ca

  • 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 [1].
  • In experiments with human SK-LMS-1 leiomyosarcoma cells, we show that the Akt kinase is activated by HGF in a time- and dose-dependent manner by phosphatidylinositol 3-kinase (PI3-kinase) [2].
  • CONCLUSIONS: Selective targeting of PI3K pathway components may enhance the effects of standard chemotherapeutic agents and provide novel adjuvant treatment of selected colorectal cancers [3].
  • Moreover, in the presence of PI 3-kinase inhibitors or pertussis toxin, not only PKB activation but also ERK1/2 activation during T. gondii infection is defective [4].
  • Our results support that this conjugate could possibly inhibit prostate cancer PC-3 cell invasion through a signaling pathway involving PI3K/Akt, alphaVbeta3/alphaVbeta5 and MMP-2/-9, and this SSA could be used as an efficient vector to deliver CPT or other cytotoxic agents to target sites for cancer therapy [5].

Psychiatry related information on Pik3ca

  • Similar to the more abundant p190 isoform, p110 myosin XVIIIA lacks a PDZ domain and, in addition, it may lack motor activity [6].

High impact information on Pik3ca

  • 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].
  • 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 [1].

Chemical compound and disease context of Pik3ca


Biological context of Pik3ca


Anatomical context of Pik3ca

  • Inhibition of PI 3-kinase activity in 3T3-L1 adipocytes resulted in abrogation of insulin-stimulated glucose uptake and thymidine incorporation [18].
  • TC21-induced alterations in cellular morphology in NIH 3T3 and PC12 cells are also PI-3K dependent [19].
  • TACC1 also cooperates with tumorigenic mutations in the PI3K pathway and thereby plays an oncogenic role in tumor formation in the murine mammary gland [20].
  • Inducible expression of Galphaq(Q209L) in a stably transfected 293 cell line caused a decrease in PI3K activity in p110alpha (but not p110beta) immunoprecipitates [21].
  • PI 3-kinase activity is required for the expression of endogenous cyclin D(1) and for S phase entry following serum stimulation of quiescent NIH 3T3 fibroblasts [22].

Associations of Pik3ca with chemical compounds

  • Surprisingly, monomeric p85 is preferentially localized to these foci compared with the p85-p110 dimer, and these foci are not sites of phosphatidylinositol-3,4,5-trisphosphate production [23].
  • Insulin stimulates glucose uptake by recruiting glucose transporter 4 (GLUT4) from an intracellular pool to the cell surface through a mechanism that is dependent on phosphatidylinositol (PI) 3-kinase (PI3-K) and cortical actin remodeling [24].
  • Class Ia phosphoinositide (PI) 3-kinase is a central component in growth factor signaling and is comprised of a p110 catalytic subunit and a regulatory subunit, the most common family of which is derived from the p85alpha gene (Pik3r1) [25].
  • Since rapamycin but not lactacystin enhances insulin-stimulated 2-deoxyglucose (2-DOG) uptake, IRS-1-associated PI 3-kinase localized at the LDM was suggested to be important in the regulation of glucose transport [26].
  • Using non-transformed androgen-sensitive epithelial cells, we show that androgens enhance the PI3-K activity by promoting accumulation of phosphoinositide-3-P phospholipids in vitro [27].

Enzymatic interactions of Pik3ca

  • In addition, immunoprecipitation of cell lysates with an antibody directed against the 85-kDa subunit of phosphatidylinositol 3-kinase (PI 3-kinase) co-precipitated a tyrosine-phosphorylated band of 180 kDa [28].

Co-localisations of Pik3ca


Regulatory relationships of Pik3ca

  • Phosphoinositide 3-kinase (PI3K) is activated by transmembrane tyrosine kinases such as vascular endothelial growth factor (VEGF) receptors and Tie2 (tunica intima endothelial kinase 2), both of which are key regulators of vascular development [30].
  • 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 [31].
  • Inhibition of PI 3-kinase by LY294002 or Deltap85 also failed to block insulin-induced reduction of resistin mRNA [32].
  • Overexpressed Smad7 also prevented ligand-induced PI3 kinase activity [33].
  • We herein examine the role of the mitogen-activated protein kinases (MAPKs) and phosphatidylinositol 3-kinase (PI-3K) cascades in the expression of the bacillus Calmette-Guerin (BCG) mycobacteria-induced NF-kappaB-dependent genes, macrophage-inflammatory protein-2 (MIP-2) and inducible nitric oxide (NO) synthase [34].

Other interactions of Pik3ca

  • Using in vitro protein kinase activity assays, it was demonstrated that heat shock stimulates c-Src and PI 3-kinase activity in a time-dependent manner [35].
  • We overexpressed Myc-tagged, membrane-targeted p110 (p110(CAAX)), and wild-type p110 (p110(WT)) in 3T3-L1 adipocytes by adenovirus-mediated gene transfer [36].
  • Experiments were designed to ask whether heat shock activates p60 c-Src tyrosine kinase or phosphatidylinositol 3-kinase (PI 3-kinase) [35].
  • Importantly, we also find that PI3K and cPKCs play a major role in the MEK-independent, prolonged MAPK activation by platelet-derived growth factor signalling [37].
  • These findings raise the possibility that PI3K may function as an upstream regulator of Tie2 expression during mouse development [30].

Analytical, diagnostic and therapeutic context of Pik3ca


  1. 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]
  2. Anti-apoptotic signaling by hepatocyte growth factor/Met via the phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pathways. Xiao, G.H., Jeffers, M., Bellacosa, A., Mitsuuchi, Y., Vande Woude , G.F., Testa, J.R. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  3. 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]
  4. Toxoplasma gondii triggers Gi-dependent PI 3-kinase signaling required for inhibition of host cell apoptosis. Kim, L., Denkers, E.Y. J. Cell. Sci. (2006) [Pubmed]
  5. A conjugate of camptothecin and a somatostatin analog against prostate cancer cell invasion via a possible signaling pathway involving PI3K/Akt, alphaVbeta3/alphaVbeta5 and MMP-2/-9. Sun, L.C., Luo, J., Mackey, L.V., Fuselier, J.A., Coy, D.H. Cancer Lett. (2007) [Pubmed]
  6. A novel 110 kDa form of myosin XVIIIA (MysPDZ) is tyrosine-phosphorylated after colony-stimulating factor-1 receptor signalling. Cross, M., Csar, X.F., Wilson, N.J., Manes, G., Addona, T.A., Marks, D.C., Whitty, G.A., Ashman, K., Hamilton, J.A. Biochem. J. (2004) [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. 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. 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]
  10. Participation of a MEK-independent pathway in MAP kinase activation and modulation of cell growth in mouse hepatoma cell lines. Saeki, Y., Hazeki, K., Hazeki, O., Ui, M., Itoh, K., Matsumoto, M., Toyoshima, K., Akedo, H., Seya, T. Int. J. Mol. Med. (2000) [Pubmed]
  11. 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]
  12. Ascorbyl stearate inhibits cell proliferation and tumor growth in human ovarian carcinoma cells by targeting the PI3K/AKT pathway. Fang, Q., Naidu, K.A., Naidu, K.A., Zhao, H., Sun, M., Dan, H.C., Nasir, A., Kaiser, H.E., Cheng, J.Q., Nicosia, S.V., Coppola, D. Anticancer Res. (2006) [Pubmed]
  13. Proliferative defect and embryonic lethality in mice homozygous for a deletion in the p110alpha subunit of phosphoinositide 3-kinase. Bi, L., Okabe, I., Bernard, D.J., Wynshaw-Boris, A., Nussbaum, R.L. J. Biol. Chem. (1999) [Pubmed]
  14. PKB-mediated negative feedback tightly regulates mitogenic signalling via Gab2. Lynch, D.K., Daly, R.J. EMBO J. (2002) [Pubmed]
  15. PTEN/MMAC1/TEP1 suppresses the tumorigenicity and induces G1 cell cycle arrest in human glioblastoma cells. Li, D.M., Sun, H. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  16. Inhibition of protein kinase B (PKB) and PKCzeta mediates keratin K10-induced cell cycle arrest. Paramio, J.M., Segrelles, C., Ruiz, S., Jorcano, J.L. Mol. Cell. Biol. (2001) [Pubmed]
  17. 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]
  18. Functional interactions of phosphatidylinositol 3-kinase with GTPase-activating protein in 3T3-L1 adipocytes. DePaolo, D., Reusch, J.E., Carel, K., Bhuripanyo, P., Leitner, J.W., Draznin, B. Mol. Cell. Biol. (1996) [Pubmed]
  19. Activation of the Ral and phosphatidylinositol 3' kinase signaling pathways by the ras-related protein TC21. Rosário, M., Paterson, H.F., Marshall, C.J. Mol. Cell. Biol. (2001) [Pubmed]
  20. Transforming acidic coiled coil 1 promotes transformation and mammary tumorigenesis. Cully, M., Shiu, J., Piekorz, R.P., Muller, W.J., Done, S.J., Mak, T.W. Cancer Res. (2005) [Pubmed]
  21. Activated G alpha q inhibits p110 alpha phosphatidylinositol 3-kinase and Akt. Ballou, L.M., Lin, H.Y., Fan, G., Jiang, Y.P., Lin, R.Z. J. Biol. Chem. (2003) [Pubmed]
  22. Multiple ras effector pathways contribute to G(1) cell cycle progression. Gille, H., Downward, J. J. Biol. Chem. (1999) [Pubmed]
  23. The p85 regulatory subunit of phosphoinositide 3-kinase down-regulates IRS-1 signaling via the formation of a sequestration complex. Luo, J., Field, S.J., Lee, J.Y., Engelman, J.A., Cantley, L.C. J. Cell Biol. (2005) [Pubmed]
  24. 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]
  25. Molecular balance between the regulatory and catalytic subunits of phosphoinositide 3-kinase regulates cell signaling and survival. Ueki, K., Fruman, D.A., Brachmann, S.M., Tseng, Y.H., Cantley, L.C., Kahn, C.R. Mol. Cell. Biol. (2002) [Pubmed]
  26. Mammalian target of rapamycin pathway regulates insulin signaling via subcellular redistribution of insulin receptor substrate 1 and integrates nutritional signals and metabolic signals of insulin. Takano, A., Usui, I., Haruta, T., Kawahara, J., Uno, T., Iwata, M., Kobayashi, M. Mol. Cell. Biol. (2001) [Pubmed]
  27. Androgen receptor mediates non-genomic activation of phosphatidylinositol 3-OH kinase in androgen-sensitive epithelial cells. Baron, S., Manin, M., Beaudoin, C., Leotoing, L., Communal, Y., Veyssiere, G., Morel, L. J. Biol. Chem. (2004) [Pubmed]
  28. ADP-ribosylation of rho p21 inhibits lysophosphatidic acid-induced protein tyrosine phosphorylation and phosphatidylinositol 3-kinase activation in cultured Swiss 3T3 cells. Kumagai, N., Morii, N., Fujisawa, K., Nemoto, Y., Narumiya, S. J. Biol. Chem. (1993) [Pubmed]
  29. A p85 subunit-independent p110alpha PI 3-kinase colocalizes with p70 S6 kinase on actin stress fibers and regulates thrombin-stimulated stress fiber formation in swiss 3T3 cells. Johanson, S.O., Naccache, P.A., Crouch, M.F. Exp. Cell Res. (1999) [Pubmed]
  30. Deficiency in the p110alpha subunit of PI3K results in diminished Tie2 expression and Tie2(-/-)-like vascular defects in mice. Lelievre, E., Bourbon, P.M., Duan, L.J., Nussbaum, R.L., Fong, G.H. Blood (2005) [Pubmed]
  31. 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]
  32. Insulin down-regulates resistin mRNA through the synthesis of protein(s) that could accelerate the degradation of resistin mRNA in 3T3-L1 adipocytes. Kawashima, J., Tsuruzoe, K., Motoshima, H., Shirakami, A., Sakai, K., Hirashima, Y., Toyonaga, T., Araki, E. Diabetologia (2003) [Pubmed]
  33. Type I transforming growth factor beta receptor binds to and activates phosphatidylinositol 3-kinase. Yi, J.Y., Shin, I., Arteaga, C.L. J. Biol. Chem. (2005) [Pubmed]
  34. Activation of phosphatidylinositol 3-kinase and c-Jun-N-terminal kinase cascades enhances NF-kappaB-dependent gene transcription in BCG-stimulated macrophages through promotion of p65/p300 binding. Darieva, Z., Lasunskaia, E.B., Campos, M.N., Kipnis, T.L., Da Silva, W.D. J. Leukoc. Biol. (2004) [Pubmed]
  35. Heat shock activates c-Src tyrosine kinases and phosphatidylinositol 3-kinase in NIH3T3 fibroblasts. Lin, R.Z., Hu, Z.W., Chin, J.H., Hoffman, B.B. J. Biol. Chem. (1997) [Pubmed]
  36. Membrane-targeted phosphatidylinositol 3-kinase mimics insulin actions and induces a state of cellular insulin resistance. Egawa, K., Sharma, P.M., Nakashima, N., Huang, Y., Huver, E., Boss, G.R., Olefsky, J.M. J. Biol. Chem. (1999) [Pubmed]
  37. Evidence for MEK-independent pathways regulating the prolonged activation of the ERK-MAP kinases. Grammer, T.C., Blenis, J. Oncogene (1997) [Pubmed]
  38. 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]
  39. Early decrease of survival factors and DNA repair enzyme in spinal motor neurons of presymptomatic transgenic mice that express a mutant SOD1 gene. Nagano, I., Murakami, T., Manabe, Y., Abe, K. Life Sci. (2002) [Pubmed]
  40. Involvement of multiple signaling pathways in diallyl sulfide mediated apoptosis in mouse skin tumors. Kalra, N., Arora, A., Shukla, Y. Asian Pac. J. Cancer Prev. (2006) [Pubmed]
  41. Role of PI3-kinase/Akt signalling pathway in renal function and cell proliferation after renal ischaemia/reperfusion injury in mice. Xie, L., Zheng, X., Qin, J., Chen, Z., Jin, Y., Ding, W. Nephrology (Carlton, Vic.) (2006) [Pubmed]
WikiGenes - Universities