Pik3ca

Summary

Gene Symbol: Pik3ca
Description: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha
Alias: 6330412C24Rik, caPI3K, p110, p110alpha, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, PI3-kinase subunit alpha, PI3K-alpha, PI3Kalpha, phosphatidylinositol 3-kinase, catalytic, alpha polypeptide, phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit alpha, phosphoinositide-3-kinase catalytic alpha polypeptide, ptdIns-3-kinase subunit alpha, ptdIns-3-kinase subunit p110-alpha, serine/threonine protein kinase PIK3CA
Species: mouse
Products:     Pik3ca

Top Publications

  1. Klippel A, Escobedo J, Hirano M, Williams L. The interaction of small domains between the subunits of phosphatidylinositol 3-kinase determines enzyme activity. Mol Cell Biol. 1994;14:2675-85 pubmed
    Previous studies have suggested that the two subunits of phosphatidylinositol (PI) 3-kinase, p85 and p110, function as localizing and catalytic subunits, respectively...
  2. Fritsch R, de Krijger I, Fritsch K, George R, Reason B, Kumar M, et al. RAS and RHO families of GTPases directly regulate distinct phosphoinositide 3-kinase isoforms. Cell. 2013;153:1050-63 pubmed publisher
    RAS proteins are important direct activators of p110?, p110?, and p110? type I phosphoinositide 3-kinases (PI3Ks), interacting via an amino-terminal RAS-binding domain (RBD)...
  3. Dou Z, Chattopadhyay M, Pan J, Guerriero J, Jiang Y, Ballou L, et al. The class IA phosphatidylinositol 3-kinase p110-beta subunit is a positive regulator of autophagy. J Cell Biol. 2010;191:827-43 pubmed publisher
    ..Here we show that the class IA p110-? catalytic subunit is a positive regulator of autophagy...
  4. Brachmann S, Ueki K, Engelman J, Kahn R, Cantley L. Phosphoinositide 3-kinase catalytic subunit deletion and regulatory subunit deletion have opposite effects on insulin sensitivity in mice. Mol Cell Biol. 2005;25:1596-607 pubmed
    ..hypersensitivity is particularly unexpected in p85alpha-/- p55alpha-/- p50alpha-/- mice, where a decrease in p110alpha and p110beta catalytic subunits was observed in insulin-sensitive tissues...
  5. Marqués M, Kumar A, Cortes I, González García A, Hernandez C, Moreno Ortiz M, et al. Phosphoinositide 3-kinases p110alpha and p110beta regulate cell cycle entry, exhibiting distinct activation kinetics in G1 phase. Mol Cell Biol. 2008;28:2803-14 pubmed publisher
    ..We show that inhibition of either p110alpha or p110beta reduced cell cycle entry. These results reveal that PI3Kalpha and -beta present distinct activation requirements and kinetics in G(1) phase, with a selective action of ..
  6. Zhao J, Cheng H, Jia S, Wang L, Gjoerup O, Mikami A, et al. The p110alpha isoform of PI3K is essential for proper growth factor signaling and oncogenic transformation. Proc Natl Acad Sci U S A. 2006;103:16296-300 pubmed
    ..Among this class of enzymes, only p110alpha, encoded by the PIK3CA gene, has been found to be mutant in human cancers...
  7. Ali K, Bilancio A, Thomas M, Pearce W, Gilfillan A, Tkaczyk C, et al. Essential role for the p110delta phosphoinositide 3-kinase in the allergic response. Nature. 2004;431:1007-11 pubmed
    ..Inactivation of p110delta protects mice against anaphylactic allergic responses. These results identify p110delta as a new target for therapeutic intervention in allergy and mast-cell-related pathologies. ..
  8. Lelievre E, Bourbon P, Duan L, Nussbaum R, Fong G. Deficiency in the p110alpha subunit of PI3K results in diminished Tie2 expression and Tie2(-/-)-like vascular defects in mice. Blood. 2005;105:3935-8 pubmed
    ..Here we demonstrate that mice deficient in the p110alpha catalytic subunit of PI3K display multiple vascular defects, including dilated vessels in the head, reduced ..
  9. Foukas L, Claret M, Pearce W, Okkenhaug K, Meek S, Peskett E, et al. Critical role for the p110alpha phosphoinositide-3-OH kinase in growth and metabolic regulation. Nature. 2006;441:366-70 pubmed
    ..To delineate the role of p110alpha, a ubiquitously expressed PI(3)K involved in tyrosine kinase and Ras signalling, here we generated mice carrying ..

More Information

Publications89

  1. Harrington L, Findlay G, Gray A, Tolkacheva T, Wigfield S, Rebholz H, et al. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J Cell Biol. 2004;166:213-23 pubmed
    ..Our results argue that the low malignant potential of tumors arising from TSC1-2 dysfunction may be explained by the failure of TSC mutant cells to activate PI3K and its downstream effectors. ..
  2. Pons S, Asano T, Glasheen E, Miralpeix M, Zhang Y, Fisher T, et al. The structure and function of p55PIK reveal a new regulatory subunit for phosphatidylinositol 3-kinase. Mol Cell Biol. 1995;15:4453-65 pubmed
    ..p55PIK forms a stable complex with p110, and it associates with IRS-1 during insulin stimulation...
  3. Utermark T, Rao T, Cheng H, Wang Q, Lee S, Wang Z, et al. The p110? and p110? isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis. Genes Dev. 2012;26:1573-86 pubmed publisher
    ..Here, we show that genetic ablation of p110? blocks tumor formation in both polyoma middle T antigen (MT) and HER2/Neu transgenic models of breast cancer...
  4. Lu Z, Jiang Y, Wang W, Xu X, Mathias R, Entcheva E, et al. Loss of cardiac phosphoinositide 3-kinase p110 alpha results in contractile dysfunction. Circulation. 2009;120:318-25 pubmed publisher
    Phosphoinositide 3-kinase (PI3K) p110alpha plays a key role in insulin action and tumorigenesis. Myocyte contraction is initiated by an inward Ca(2+) current (I(Ca,L)) through the voltage-dependent L-type Ca(2+) channel (LTCC)...
  5. Knight Z, Gonzalez B, Feldman M, Zunder E, Goldenberg D, Williams O, et al. A pharmacological map of the PI3-K family defines a role for p110alpha in insulin signaling. Cell. 2006;125:733-47 pubmed
    ..This chemical array was then used to define the PI3-K isoforms required for insulin signaling. We find that p110alpha is the primary insulin-responsive PI3-K in cultured cells, whereas p110beta is dispensable but sets a phenotypic ..
  6. Bi L, Okabe I, Bernard D, Nussbaum R. Early embryonic lethality in mice deficient in the p110beta catalytic subunit of PI 3-kinase. Mamm Genome. 2002;13:169-72 pubmed
  7. Bi L, Okabe I, Bernard D, Wynshaw Boris A, Nussbaum R. Proliferative defect and embryonic lethality in mice homozygous for a deletion in the p110alpha subunit of phosphoinositide 3-kinase. J Biol Chem. 1999;274:10963-8 pubmed
    ..cells, we deleted this binding domain in the gene encoding the alpha isoform of the 110-kDa catalytic subunit (Pik3ca) of the alpha isozyme of the type IA kinases, leading to loss of expression of the p110 catalytic subunit...
  8. Shioi T, Kang P, Douglas P, Hampe J, Yballe C, Lawitts J, et al. The conserved phosphoinositide 3-kinase pathway determines heart size in mice. EMBO J. 2000;19:2537-48 pubmed
    ..Thus, the PI3K pathway is necessary and sufficient to promote organ growth in mammals. ..
  9. Sopasakis V, Liu P, Suzuki R, Kondo T, Winnay J, Tran T, et al. Specific roles of the p110alpha isoform of phosphatidylinsositol 3-kinase in hepatic insulin signaling and metabolic regulation. Cell Metab. 2010;11:220-30 pubmed publisher
    ..Using tissue-specific gene inactivation, we demonstrate that p110alpha catalytic subunit of PI3K is a key mediator of insulin metabolic actions in the liver...
  10. Yang H, Shin M, Lee S, Kim J, Park W, Cho K, et al. Cooperative activation of PI3K by Ras and Rho family small GTPases. Mol Cell. 2012;47:281-90 pubmed publisher
    ..five homologous Ras family small GTPases function upstream of PI3K by directly binding the PI3K catalytic subunit, p110. In contrast, several Rho family small GTPases activated PI3K by an indirect cooperative positive feedback that ..
  11. Ballou L, Lin H, Fan G, Jiang Y, Lin R. Activated G alpha q inhibits p110 alpha phosphatidylinositol 3-kinase and Akt. J Biol Chem. 2003;278:23472-9 pubmed
    ..expression of Galphaq(Q209L) in a stably transfected 293 cell line caused a decrease in PI3K activity in p110alpha (but not p110beta) immunoprecipitates...
  12. Foukas L, Berenjeno I, Gray A, Khwaja A, Vanhaesebroeck B. Activity of any class IA PI3K isoform can sustain cell proliferation and survival. Proc Natl Acad Sci U S A. 2010;107:11381-6 pubmed publisher
    Small molecule inhibitors of PI3K for oncology mainly target the class I PI3Ks, comprising the p110alpha, beta, gamma, and delta isoforms, of which only p110alpha is mutated in cancer...
  13. Gupta S, Ramjaun A, Haiko P, Wang Y, Warne P, Nicke B, et al. Binding of ras to phosphoinositide 3-kinase p110alpha is required for ras-driven tumorigenesis in mice. Cell. 2007;129:957-68 pubmed
    ..Here we generate mice with mutations in the Pi3kca gene encoding the catalytic p110alpha isoform that block its interaction with Ras...
  14. Renner O, Blanco Aparicio C, Grassow M, Canamero M, Leal J, Carnero A. Activation of phosphatidylinositol 3-kinase by membrane localization of p110alpha predisposes mammary glands to neoplastic transformation. Cancer Res. 2008;68:9643-53 pubmed publisher
    ..Enhanced activation of p110alpha, the catalytic subunit of PI3K, was found in a high proportion of many human tumor types...
  15. Inuzuka Y, Okuda J, Kawashima T, Kato T, Niizuma S, Tamaki Y, et al. Suppression of phosphoinositide 3-kinase prevents cardiac aging in mice. Circulation. 2009;120:1695-703 pubmed publisher
    ..We analyzed age-associated changes in murine heart and the manner in which suppression of the p110alpha isoform of phosphoinositide 3-kinase activity modified cardiac aging...
  16. Dubois E, Jacoby M, Blockmans M, Pernot E, Schiffmann S, Foukas L, et al. Developmental defects and rescue from glucose intolerance of a catalytically-inactive novel Ship2 mutant mouse. Cell Signal. 2012;24:1971-80 pubmed publisher
    ..We expected that the expression of the catalytically inactive Ship2 protein in PI 3'-kinase-defective p110?(D933A/+) mice would counterbalance the phenotypes of parental mice by restoring normal PKB signaling but, for most ..
  17. Graupera M, Guillermet Guibert J, Foukas L, Phng L, Cain R, Salpekar A, et al. Angiogenesis selectively requires the p110alpha isoform of PI3K to control endothelial cell migration. Nature. 2008;453:662-6 pubmed publisher
    ..Class IA PI3K isoforms couple to tyrosine kinases and consist of a p110 catalytic subunit (p110alpha, p110beta or p110delta), constitutively bound to one of five distinct p85 regulatory subunits...
  18. Jia S, Liu Z, Zhang S, Liu P, Zhang L, Lee S, et al. Essential roles of PI(3)K-p110beta in cell growth, metabolism and tumorigenesis. Nature. 2008;454:776-9 pubmed publisher
    On activation by receptors, the ubiquitously expressed class IA isoforms (p110alpha and p110beta) of phosphatidylinositol-3-OH kinase (PI(3)K) generate lipid second messengers, which initiate multiple signal transduction cascades...
  19. Papakonstanti E, Zwaenepoel O, Bilancio A, Burns E, Nock G, Houseman B, et al. Distinct roles of class IA PI3K isoforms in primary and immortalised macrophages. J Cell Sci. 2008;121:4124-33 pubmed publisher
    The class IA isoforms of phosphoinositide 3-kinase (p110alpha, p110beta and p110delta) often have non-redundant functions in a given cell type...
  20. Pretorius L, Du X, Woodcock E, Kiriazis H, Lin R, Marasco S, et al. Reduced phosphoinositide 3-kinase (p110alpha) activation increases the susceptibility to atrial fibrillation. Am J Pathol. 2009;175:998-1009 pubmed publisher
    ..The purpose of this study was to assess whether reduced activation of phosphoinositide 3-kinase (PI3K, p110alpha) makes the compromised heart susceptible to AF...
  21. Al Qassab H, Smith M, Irvine E, Guillermet Guibert J, Claret M, Choudhury A, et al. Dominant role of the p110beta isoform of PI3K over p110alpha in energy homeostasis regulation by POMC and AgRP neurons. Cell Metab. 2009;10:343-54 pubmed publisher
    ..We inactivated either p110alpha or p110beta PI3K catalytic subunits in these neurons and demonstrate a dominant role for the latter in energy ..
  22. Lindmo K, Stenmark H. Regulation of membrane traffic by phosphoinositide 3-kinases. J Cell Sci. 2006;119:605-14 pubmed
    ..By contrast, class III PI 3-kinases mainly mediate receptor-independent trafficking events, which mostly are related to endocytic membrane traffic, phagosome maturation and autophagy. ..
  23. Tikoo A, Roh V, Montgomery K, Ivetac I, Waring P, Pelzer R, et al. Physiological levels of Pik3ca(H1047R) mutation in the mouse mammary gland results in ductal hyperplasia and formation of ER?-positive tumors. PLoS ONE. 2012;7:e36924 pubmed publisher
    b>PIK3CA, the gene coding for the p110? subunit of phosphoinositide 3-kinase, is frequently mutated in a variety of human tumors including breast cancers...
  24. Drakas R, Tu X, Baserga R. Control of cell size through phosphorylation of upstream binding factor 1 by nuclear phosphatidylinositol 3-kinase. Proc Natl Acad Sci U S A. 2004;101:9272-6 pubmed
    ..here that IRS-1 binds also to the phosphatidylinositol 3-kinase (PI3-K) subunits in nuclear extracts, and that the p110 subunit of PI3-K directly phosphorylates and activates UBF1, an exclusively nucleolar protein...
  25. Foukas L, Bilanges B, Bettedi L, Pearce W, Ali K, Sancho S, et al. Long-term p110α PI3K inactivation exerts a beneficial effect on metabolism. EMBO Mol Med. 2013;5:563-71 pubmed publisher
    ..Gain-of-function mutations in p110α, the principal mammalian IIS-responsive isoform of PI 3-kinase (PI3K), promote cancer...
  26. Acosta Y, Zafra M, Ojeda G, Bernardone I, Dianzani U, Portoles P, et al. Biased binding of class IA phosphatidyl inositol 3-kinase subunits to inducible costimulator (CD278). Cell Mol Life Sci. 2011;68:3065-79 pubmed publisher
    ..ICOS binds class IA phosphatidyl inositol 3-kinase (PI3-K) p85?, p50-55? and p85? regulatory subunits and p110?, p110? and p110? catalytic subunits...
  27. Utermark T, Schmit F, Lee S, Gao X, Schaffhausen B, Roberts T. The phosphatidylinositol 3-kinase (PI3K) isoform dependence of tumor formation is determined by the genetic mode of PI3K pathway activation rather than by tissue type. J Virol. 2014;88:10673-9 pubmed publisher
    Previous work has shown that prostate cancer in a Pten-null murine model is dependent on the p110? isoform of phosphatidylinositol 3-kinase (PI3K), while breast cancer driven by either polyoma middle T antigen (MT) or HER2 is p110? ..
  28. Tacheau C, Fontaine J, Loy J, Mauviel A, Verrecchia F. TGF-beta induces connexin43 gene expression in normal murine mammary gland epithelial cells via activation of p38 and PI3K/AKT signaling pathways. J Cell Physiol. 2008;217:759-68 pubmed publisher
  29. Stratikopoulos E, Dendy M, Szabolcs M, Khaykin A, Lefebvre C, Zhou M, et al. Kinase and BET Inhibitors Together Clamp Inhibition of PI3K Signaling and Overcome Resistance to Therapy. Cancer Cell. 2015;27:837-51 pubmed publisher
    ..Combined PI3K and BET inhibition induced cell death, tumor regression, and clamped inhibition of PI3K signaling in a broad range of tumor cell lines to provide a strategy to overcome resistance to kinase inhibitor therapy. ..
  30. Popkie A, Zeidner L, Albrecht A, D Ippolito A, Eckardt S, Newsom D, et al. Phosphatidylinositol 3-kinase (PI3K) signaling via glycogen synthase kinase-3 (Gsk-3) regulates DNA methylation of imprinted loci. J Biol Chem. 2010;285:41337-47 pubmed publisher
    ..Finally, we find that N-Myc is a potent Gsk-3-dependent regulator of Dnmt3a2 expression. In summary, we have identified a signal transduction pathway that is capable of altering the DNA methylation of imprinted loci. ..
  31. Zhai Y, Kuick R, Tipton C, Wu R, Sessine M, Wang Z, et al. Arid1a inactivation in an Apc- and Pten-defective mouse ovarian cancer model enhances epithelial differentiation and prolongs survival. J Pathol. 2016;238:21-30 pubmed publisher
    ..We also found that an activating (E545K) Pik3ca mutation, unlike Pten inactivation or Pik3ca H1047R mutation, cannot cooperate with Arid1a loss to promote ovarian ..
  32. Huang B, Lin C, Chen H, Lin J, Cheng Y, Kao S. AMPK activation inhibits expression of proinflammatory mediators through downregulation of PI3K/p38 MAPK and NF-κB signaling in murine macrophages. DNA Cell Biol. 2015;34:133-41 pubmed publisher
  33. Chaudhari A, Krumlinde D, Lundqvist A, Akyürek L, Bandaru S, Skålén K, et al. p110α Hot Spot Mutations E545K and H1047R Exert Metabolic Reprogramming Independently of p110α Kinase Activity. Mol Cell Biol. 2015;35:3258-73 pubmed publisher
    The phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) catalytic subunit p110α is the most frequently mutated kinase in human cancer, and the hot spot mutations E542K, E545K, and H1047R are the most common mutations in p110α...
  34. Liu T, Shi C, Gao R, Sun H, Xiong X, Ding L, et al. Irisin inhibits hepatic gluconeogenesis and increases glycogen synthesis via the PI3K/Akt pathway in type 2 diabetic mice and hepatocytes. Clin Sci (Lond). 2015;129:839-50 pubmed publisher
    ..phosphorylation; it prevented GlcN-induced decreases in glycogen content and the phosphoinositide 3-kinase (PI3K) p110α subunit level, and the phosphorylation of Akt/protein kinase B, forkhead box transcription factor O1 (FOXO1) ..
  35. Abba M, Zhong Y, Lee J, Kil H, Lu Y, Takata Y, et al. DMBA induced mouse mammary tumors display high incidence of activating Pik3caH1047 and loss of function Pten mutations. Oncotarget. 2016;7:64289-64299 pubmed publisher
    ..Eighty-two percent (9/11) of tumors carried the Pik3ca H1047L/R hot-spot mutation, as frequently found in human breast cancer...
  36. Berenjeno I, Guillermet Guibert J, Pearce W, Gray A, Fleming S, Vanhaesebroeck B. Both p110? and p110? isoforms of PI3K can modulate the impact of loss-of-function of the PTEN tumour suppressor. Biochem J. 2012;442:151-9 pubmed publisher
    ..PTEN is a phosphatase with selectivity for PtdIns(3,4,5)P3, which is produced by the class I isoforms of PI3K (p110?, p110?, p110? and p110?)...
  37. Aksoy I, Ramsey M, Fruman D, Aksoy S, Cantley L, Tucker J, et al. Mouse phosphoinositide 3-kinase p110alpha gene: cloning, structural organization, and localization to chromosome 3 band B. Biochem Biophys Res Commun. 1999;262:438-42 pubmed
    ..cDNAs for three mammalian Class IA PI3-Kinase catalytic subunits designated p110alpha, p110beta, and p110delta have been cloned from several species...
  38. Lee C, Sukhumavasi W, Denkers E. Phosphoinositide-3-kinase-dependent, MyD88-independent induction of CC-type chemokines characterizes the macrophage response to Toxoplasma gondii strains with high virulence. Infect Immun. 2007;75:5788-97 pubmed
  39. Chen S, Burgin S, McDaniel A, Li X, Yuan J, Chen M, et al. Nf1-/- Schwann cell-conditioned medium modulates mast cell degranulation by c-Kit-mediated hyperactivation of phosphatidylinositol 3-kinase. Am J Pathol. 2010;177:3125-32 pubmed publisher
    ..Collectively, these studies identify both c-Kit and PI3K as molecular targets that modulate mast cell functions in cases of NF1. ..
  40. Krishnan S, Mali R, Ramdas B, Sims E, Ma P, Ghosh J, et al. p85? regulatory subunit of class IA PI3 kinase negatively regulates mast cell growth, maturation, and leukemogenesis. Blood. 2012;119:3951-61 pubmed publisher
    ..Thus, p85? and p85? differentially regulate SCF and oncogenic KIT-induced signals in myeloid lineage-derived mast cells. ..
  41. Matheny R, Abdalla M, Geddis A, Leandry L, Lynch C. Skeletal muscle PI3K p110? regulates expression of AMP-activated protein kinase. Biochem Biophys Res Commun. 2017;482:1420-1426 pubmed publisher
    ..Given this lack of knowledge, we performed a series of experiments to define the extent to which PI3K p110? mediated expression and (or) activation of AMPK in skeletal muscle...
  42. Kudo Y, Tanaka Y, Tateishi K, Yamamoto K, Yamamoto S, Mohri D, et al. Altered composition of fatty acids exacerbates hepatotumorigenesis during activation of the phosphatidylinositol 3-kinase pathway. J Hepatol. 2011;55:1400-8 pubmed publisher
    ..We established hepatocyte-specific Pik3ca transgenic (Tg) mice harboring N1068fs*4 mutation. The Tg mice exhibited hepatic steatosis and tumor development...
  43. Kim S, Ebbert K, Cordeiro M, Romero M, Whelan K, Suarez A, et al. Constitutive Activation of PI3K in Oocyte Induces Ovarian Granulosa Cell Tumors. Cancer Res. 2016;76:3851-61 pubmed publisher
    ..Cancer Res; 76(13); 3851-61. ©2016 AACR. ..
  44. Perkinton M, Ip J, Wood G, Crossthwaite A, Williams R. Phosphatidylinositol 3-kinase is a central mediator of NMDA receptor signalling to MAP kinase (Erk1/2), Akt/PKB and CREB in striatal neurones. J Neurochem. 2002;80:239-54 pubmed
    ..We propose that NMDA receptor stimulation can activate Erk1/2 and Akt signalling pathways in a PI 3-kinase dependent manner which may target CREB in the nucleus. ..
  45. Vantler M, Jesus J, Leppänen O, Scherner M, Berghausen E, Mustafov L, et al. Class IA Phosphatidylinositol 3-Kinase Isoform p110α Mediates Vascular Remodeling. Arterioscler Thromb Vasc Biol. 2015;35:1434-44 pubmed publisher
    ..to systematically characterize the precise role of catalytic class IA phosphatidylinositol 3'-kinase isoforms (p110α, p110β, p110δ), which signal downstream of receptor tyrosine kinases, for vascular remodeling in vivo...
  46. Nelson V, Negrón A, Reid I, Thomas J, Yang L, Lin R, et al. Loss of PI3K p110? in the Adipose Tissue Results in Infertility and Delayed Puberty Onset in Male Mice. Biomed Res Int. 2017;2017:3756089 pubmed publisher
    Deletion of PI3K catalytic subunit p110? in adipose tissue (aP2-Cre/p110?flx/flx, ?-/- hereafter) results in increased adiposity, glucose intolerance, and liver steatosis...
  47. Zhang T, Yao Y, Wang J, Li Y, He P, Pasupuleti V, et al. Haploinsufficiency of Klippel-Trenaunay syndrome gene Aggf1 inhibits developmental and pathological angiogenesis by inactivating PI3K and AKT and disrupts vascular integrity by activating VE-cadherin. Hum Mol Genet. 2016;25:5094-5110 pubmed publisher
    ..Together with recent identification of somatic mutations in p110? (encoded by PIK3CA), our data establish a potential mechanistic link between AGGF1 and PIK3CA, the two genes identified for KTS.
  48. Ko H, Kim C, Lee S, Song J, Lee K, Kim K, et al. P42 Ebp1 regulates the proteasomal degradation of the p85 regulatory subunit of PI3K by recruiting a chaperone-E3 ligase complex HSP70/CHIP. Cell Death Dis. 2014;5:e1131 pubmed publisher
    ..Thus, the tumor-suppressing effects of p42 in cancer cells are driven by negative regulation of the p85 subunit of PI3K. ..
  49. Hanker A, Pfefferle A, Balko J, Kuba M, Young C, Sanchez V, et al. Mutant PIK3CA accelerates HER2-driven transgenic mammary tumors and induces resistance to combinations of anti-HER2 therapies. Proc Natl Acad Sci U S A. 2013;110:14372-7 pubmed publisher
    ..2 (HER2; ERBB2) amplification and phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) mutations often co-occur in breast cancer...
  50. Liu H, Shi H, Zhao X, Zhang R, Liu G, Zhang J. The TLR3, PI3K, survivin, FasL, and Fas genes as major risk factors of occurrence and development of cervical cancer disease. Gene. 2014;550:27-32 pubmed publisher
    ..This study demonstrates that TLR3-siRNA and LY294002 treatments can markedly suppress cervical cancer cell invasion and tumor growth and increase survival life by silencing targeted genes. ..
  51. Li X, Tao J, Cigliano A, Sini M, Calderaro J, Azoulay D, et al. Co-activation of PIK3CA and Yap promotes development of hepatocellular and cholangiocellular tumors in mouse and human liver. Oncotarget. 2015;6:10102-15 pubmed
    ..carcinogenesis, we generated a mouse model characterized by combined overexpression of activated mutant forms of PIK3CA (PIK3CAH1047R) and Yap (YapS127A) in the mouse liver using hydrodynamic transfection (PIK3CA/Yap)...
  52. Deuker M, Marsh Durban V, Phillips W, McMahon M. PI3'-kinase inhibition forestalls the onset of MEK1/2 inhibitor resistance in BRAF-mutated melanoma. Cancer Discov. 2015;5:143-53 pubmed publisher
    ..occurs via silencing of the PI3'-lipid phosphatase PTEN or, less commonly, through mutational activation of PIK3CA, encoding the 110-kDa catalytic subunit of PI3'-kinase-α (PI3Kα)...
  53. Xu X, Zhang Z, Su W, Zhang Y, Feng C, Zhao H, et al. Involvement of the p110 alpha isoform of PI3K in early development of mouse embryos. Mol Reprod Dev. 2009;76:389-98 pubmed publisher
    ..paper, mouse one-cell embryos were used to investigate a possible contribution of the catalytic subunit of PI3K, p110 alpha, to cell cycle progression...
  54. Voisinne G, García Blesa A, Chaoui K, Fiore F, Bergot E, Girard L, et al. Co-recruitment analysis of the CBL and CBLB signalosomes in primary T cells identifies CD5 as a key regulator of TCR-induced ubiquitylation. Mol Syst Biol. 2016;12:876 pubmed publisher
    ..Our results offer an integrated view of the CBL and CBLB signaling complexes induced by TCR stimulation and provide a molecular basis for their negative regulatory function in normal T cells. ..
  55. Cizmecioglu O, Ni J, Xie S, Zhao J, Roberts T. Rac1-mediated membrane raft localization of PI3K/p110? is required for its activation by GPCRs or PTEN loss. elife. 2016;5: pubmed publisher
    ..membrane might contribute to the functions of the ubiquitous class IA phosphoinositide 3-kinase (PI3K) isoforms, p110? and p110?. We found that p110? localizes to membrane rafts in a Rac1-dependent manner...
  56. Ritchie R, Love J, Huynh K, Bernardo B, Henstridge D, Kiriazis H, et al. Enhanced phosphoinositide 3-kinase(p110?) activity prevents diabetes-induced cardiomyopathy and superoxide generation in a mouse model of diabetes. Diabetologia. 2012;55:3369-81 pubmed publisher
    ..male cardiac-specific transgenic mice with increased PI3K(p110?) activity (constitutively active PI3K [p110?], caPI3K] or decreased PI3K(p110?) activity (dominant-negative PI3K [p110?], dnPI3K) and non-transgenic (Ntg) mice for 12 ..
  57. Pimentel B, Rodríguez Borlado L, Hernandez C, Carrera A. A Role for phosphoinositide 3-kinase in the control of cell division and survival during retinal development. Dev Biol. 2002;247:295-306 pubmed
    ..b>p110alpha has been shown to regulate cell division and survival...
  58. Takahashi H, Okamura D, Starr M, Saito H, Evers B. Age-dependent reduction of the PI3K regulatory subunit p85? suppresses pancreatic acinar cell proliferation. Aging Cell. 2012;11:305-14 pubmed publisher
  59. Elsawa S, Almada L, Ziesmer S, Novak A, Witzig T, Ansell S, et al. GLI2 transcription factor mediates cytokine cross-talk in the tumor microenvironment. J Biol Chem. 2011;286:21524-34 pubmed publisher
    ..Together, these results identify a novel signaling pathway mediating the stromal-cancer cell interactions, leading to increased Ig production by malignant cells. ..
  60. So L, Yea S, Oak J, Lu M, Manmadhan A, Ke Q, et al. Selective inhibition of phosphoinositide 3-kinase p110? preserves lymphocyte function. J Biol Chem. 2013;288:5718-31 pubmed publisher
    ..The p110? catalytic isoform of PI3K is highly expressed in lymphocytes and plays a prominent role in B and T cell responses...
  61. CAROMILE L, Dortche K, Rahman M, Grant C, Stoddard C, Ferrer F, et al. PSMA redirects cell survival signaling from the MAPK to the PI3K-AKT pathways to promote the progression of prostate cancer. Sci Signal. 2017;10: pubmed publisher
  62. Yu X, Wu Q, Wang L, Zhao Y, Zhang Q, Meng Q, et al. Silencing of ST6GalNAc I suppresses the proliferation, migration and invasion of hepatocarcinoma cells through PI3K/AKT/NF-?B pathway. Tumour Biol. 2016;37:12213-12221 pubmed
  63. San Miguel S, Serrano M, Sachar A, Henkemeyer M, Svoboda K, Benson M. Ephrin reverse signaling controls palate fusion via a PI3 kinase-dependent mechanism. Dev Dyn. 2011;240:357-64 pubmed publisher
    ..Thus, ephrin reverse signaling is necessary and sufficient to induce palate fusion independent of TGF?3. These data describe both a novel role for ephrins in palate morphogenesis, and a previously unknown mechanism of ephrin signaling...
  64. Joshi A, Ellenson L. PI3K/PTEN/AKT Genetic Mouse Models of Endometrial Carcinoma. Adv Exp Med Biol. 2017;943:261-273 pubmed
    ..Additional events like mutations in Pik3ca or mismatch repair deficiency are required for progression to carcinoma...
  65. Silio V, Redondo Muñoz J, Carrera A. Phosphoinositide 3-kinase ? regulates chromosome segregation in mitosis. Mol Biol Cell. 2012;23:4526-42 pubmed publisher
    Class I(A) phosphoinositide 3-kinases (PI3K) are enzymes composed of a p85 regulatory and a p110 catalytic subunit that control formation of 3-poly-phosphoinositides (PIP(3))...
  66. De Blasio M, Huynh K, Qin C, Rosli S, Kiriazis H, Ayer A, et al. Therapeutic targeting of oxidative stress with coenzyme Q10 counteracts exaggerated diabetic cardiomyopathy in a mouse model of diabetes with diminished PI3K(p110α) signaling. Free Radic Biol Med. 2015;87:137-47 pubmed publisher
    ..We previously demonstrated that LV phosphoinositide 3-kinase p110α (PI3K) protects the heart against diabetic cardiomyopathy, associated with reduced NADPH oxidase expression and ..
  67. Juvekar A, Hu H, Yadegarynia S, Lyssiotis C, Ullas S, Lien E, et al. Phosphoinositide 3-kinase inhibitors induce DNA damage through nucleoside depletion. Proc Natl Acad Sci U S A. 2016;113:E4338-47 pubmed publisher
    ..In this mouse model, combined PI3K and PARP inhibition was superior to either agent alone to induce durable remissions of established tumors. ..
  68. Yokoyama K, Tezuka T, Kotani M, Nakazawa T, Hoshina N, Shimoda Y, et al. NYAP: a phosphoprotein family that links PI3K to WAVE1 signalling in neurons. EMBO J. 2011;30:4739-54 pubmed publisher
    ..In conclusion, the NYAPs activate PI3K and concomitantly recruit the downstream effector WAVE complex to the close vicinity of PI3K and regulate neuronal morphogenesis. ..
  69. Prasad R, Vaid M, Katiyar S. Grape proanthocyanidin inhibit pancreatic cancer cell growth in vitro and in vivo through induction of apoptosis and by targeting the PI3K/Akt pathway. PLoS ONE. 2012;7:e43064 pubmed publisher
    ..Together, these results suggest that GSPs may have a potential chemotherapeutic effect on pancreatic cancer cell growth. ..
  70. McLean B, Kienesberger P, Wang W, Masson G, Zhabyeyev P, Dyck J, et al. Enhanced recovery from ischemia-reperfusion injury in PI3K? dominant negative hearts: investigating the role of alternate PI3K isoforms, increased glucose oxidation and MAPK signaling. J Mol Cell Cardiol. 2013;54:9-18 pubmed publisher
    ..by which PI3K?DN hearts are protected from IR injury, we created a double mutant (PI3KDM) model by crossing p110?(-/-) (PI3K?KO) with cardiac-specific PI3K?DN mice...
  71. Wu C, Jia Z, Wang W, Ballou L, Jiang Y, Chen B, et al. PI3Ks maintain the structural integrity of T-tubules in cardiac myocytes. PLoS ONE. 2011;6:e24404 pubmed publisher
    ..Genetic ablation of both p110? and p110? in cardiac myocytes throughout development or in adult mice caused heart failure and death...
  72. Lee W, Kim H, Seok J, Jang H, Park Y, Kim S, et al. Genomic profiling of patient-derived colon cancer xenograft models. Medicine (Baltimore). 2014;93:e298 pubmed publisher
    ..However, 2 PDX models showed gained mutations such as PIK3CA or FBWX7 mutation. Ten patient-derived advanced colon cancer xenograft models were established...
  73. Trivedi P, Yang R, Barouch L. Decreased p110alpha catalytic activity accompanies increased myocyte apoptosis and cardiac hypertrophy in leptin deficient ob/ob mice. Cell Cycle. 2008;7:560-5 pubmed
    ..Here we further show that ob/ob mice have decreased catalytic activity of phosphoinositide 3-kinase (PI3K) (p110alpha) which is reversed with leptin treatment...
  74. Westernberg L, Conche C, Huang Y, Rigaud S, Deng Y, Siegemund S, et al. Non-canonical antagonism of PI3K by the kinase Itpkb delays thymocyte β-selection and renders it Notch-dependent. elife. 2016;5: pubmed publisher
    ..This is reversed by inhibition of Akt, mTOR or glucose metabolism. Thus, non-canonical PI3K-antagonism by Itpkb restricts pre-TCR induced metabolic activation to enforce coincidence-detection of pre-TCR expression and Notch-engagement. ..
  75. Liu W, Cao H, Ye C, Chang C, Lu M, Jing Y, et al. Hepatic miR-378 targets p110α and controls glucose and lipid homeostasis by modulating hepatic insulin signalling. Nat Commun. 2014;5:5684 pubmed publisher
    ..miR-378 inhibits hepatic insulin signalling through targeting p110α, a subunit of PI3K and hence a critical component of insulin signalling...
  76. Cheng H, Zhang X, Su J, Li Q. [Study of gambogenic acid-induced apoptosis of melanoma B16 cells through PI3K/Akt/mTOR signaling pathways]. Zhongguo Zhong Yao Za Zhi. 2014;39:1666-9 pubmed
    ..GNA could inhibit the proliferation of melanoma B16 cells and induce their apoptosis within certain time and concentration ranges. Its mechanism in inducing the cell apoptosis may be related to PI3K/Akt/mTOR signaling pathways. ..
  77. Aragoneses Fenoll L, Montes Casado M, Ojeda G, Acosta Y, Herranz J, Martínez S, et al. ETP-46321, a dual p110α/δ class IA phosphoinositide 3-kinase inhibitor modulates T lymphocyte activation and collagen-induced arthritis. Biochem Pharmacol. 2016;106:56-69 pubmed publisher
    ..T lymphocytes express high levels of p110α and p110δ class IA PI3K...
  78. Chandler R, Damrauer J, Raab J, Schisler J, Wilkerson M, Didion J, et al. Coexistent ARID1A-PIK3CA mutations promote ovarian clear-cell tumorigenesis through pro-tumorigenic inflammatory cytokine signalling. Nat Commun. 2015;6:6118 pubmed publisher
    ..for tumour formation, but requires concurrent activation of the phosphoinositide 3-kinase catalytic subunit, PIK3CA. Remarkably, the mice develop highly penetrant tumours with OCCC-like histopathology, culminating in haemorrhagic ..
  79. Hon W, Berndt A, Williams R. Regulation of lipid binding underlies the activation mechanism of class IA PI3-kinases. Oncogene. 2012;31:3655-66 pubmed publisher
    Somatic missense mutations in PIK3CA, which encodes the p110? catalytic subunit of phosphoinositide 3-kinases, occur frequently in human cancers...
  80. Deming D, Leystra A, Nettekoven L, Sievers C, Miller D, Middlebrooks M, et al. PIK3CA and APC mutations are synergistic in the development of intestinal cancers. Oncogene. 2014;33:2245-54 pubmed publisher
    ..Polyposis Coli (APC) gene is mutated in the majority of human colon cancers and often occurs simultaneously with PIK3CA mutations, we sought to better understand the interaction between APC and PIK3CA mutations in the mammalian ..