Gene Symbol: Pik3ca
Description: phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha
Alias: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, PI3-kinase subunit alpha, PI3K-alpha, PI3Kalpha, p110alpha, 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: rat
Products:     Pik3ca

Top Publications

  1. Franke T. PI3K/Akt: getting it right matters. Oncogene. 2008;27:6473-88 pubmed publisher
    ..An emphasis is placed on the involvement of Akt in human diseases ranging from cancer to metabolic dysfunction and mental disease. ..
  2. Antonetti D, Algenstaedt P, Kahn C. Insulin receptor substrate 1 binds two novel splice variants of the regulatory subunit of phosphatidylinositol 3-kinase in muscle and brain. Mol Cell Biol. 1996;16:2195-203 pubmed
  3. Schubert M, Brazil D, Burks D, Kushner J, Ye J, Flint C, et al. Insulin receptor substrate-2 deficiency impairs brain growth and promotes tau phosphorylation. J Neurosci. 2003;23:7084-92 pubmed
    ..Thus, dysregulation of the Irs2 branch of the insulin-Igf-signaling cascade reveals a molecular link between diabetes and neurodegenerative disease. ..
  4. Hare L, Schwarz Q, Wiszniak S, Gurung R, Montgomery K, Mitchell C, et al. Heterozygous expression of the oncogenic Pik3ca(H1047R) mutation during murine development results in fatal embryonic and extraembryonic defects. Dev Biol. 2015;404:14-26 pubmed publisher
    ..Somatic mutations in PIK3CA, the gene encoding the p110α catalytic subunit of PI3K enzyme, are commonly associated with many human cancers ..
  5. Engelman J, Luo J, Cantley L. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet. 2006;7:606-19 pubmed
    ..In light of the recent advances in our understanding of the function of PI3Ks in the pathogenesis of diabetes and cancer, we discuss the exciting therapeutic opportunities for targeting this pathway to treat these diseases. ..
  6. Slattery M, Herrick J, Lundgreen A, Fitzpatrick F, Curtin K, Wolff R. Genetic variation in a metabolic signaling pathway and colon and rectal cancer risk: mTOR, PTEN, STK11, RPKAA1, PRKAG2, TSC1, TSC2, PI3K and Akt1. Carcinogenesis. 2010;31:1604-11 pubmed publisher
    ..3 tagSNPs), PTEN (9 tagSNPs), FRAP1 (mTOR) (4 tagSNPs), TSC1 (14 tagSNPs), TSC2 (8 tagSNPs), Akt1 (2 tagSNPs), PIK3CA (7 tagSNPs), PRKAA1 (13 tagSNPs) and PRKAG2 (68 tagSNPs) in two population-based case-control studies of colon (n =..
  7. Kinross K, Montgomery K, Kleinschmidt M, Waring P, Ivetac I, Tikoo A, et al. An activating Pik3ca mutation coupled with Pten loss is sufficient to initiate ovarian tumorigenesis in mice. J Clin Invest. 2012;122:553-7 pubmed publisher
    Mutations in the gene encoding the p110? subunit of PI3K (PIK3CA) that result in enhanced PI3K activity are frequently observed in human cancers...
  8. Baptista I, Silva W, Artioli G, Guilherme J, Leal M, Aoki M, et al. Leucine and HMB differentially modulate proteasome system in skeletal muscle under different sarcopenic conditions. PLoS ONE. 2013;8:e76752 pubmed publisher
    ..On the other hand, HMB treatment failed to maintain tetanic peak force regardless of treatment. The present data suggested that the anti-atrophic effects of leucine are not mediated by its metabolite HMB. ..
  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


  1. Choi W, Sung C. Characterization of insulin receptor substrate 3 in rat liver derived cells. Biochem Biophys Res Commun. 2000;272:953-8 pubmed
    ..Unlike related IRS-1/2 that is transiently phosphorylated, IRS-3 shows robust and prolonged tyrosine phosphorylation upon insulin treatment of cells and may play a role in delayed and/or prolonged insulin actions. ..
  2. Lu W, Bhasin M, Tsirka S. Involvement of tissue plasminogen activator in onset and effector phases of experimental allergic encephalomyelitis. J Neurosci. 2002;22:10781-9 pubmed
    ..A temporally restricted attenuation of tPA activity could have therapeutic potential in the management of MS. ..
  3. Hirsch E, Costa C, Ciraolo E. Phosphoinositide 3-kinases as a common platform for multi-hormone signaling. J Endocrinol. 2007;194:243-56 pubmed
    ..This review will thus focus on the different pathways that converge on PI3K activation, with particular attention to the paradigmatic PI3K involvement in insulin signaling. ..
  4. Jiang Y, Chang G, Wang Y, Zhang D, Cao L, Liu J. Geniposide Prevents Hypoxia/Reoxygenation-Induced Apoptosis in H9c2 Cells: Improvement of Mitochondrial Dysfunction and Activation of GLP-1R and the PI3K/AKT Signaling Pathway. Cell Physiol Biochem. 2016;39:407-21 pubmed publisher
    ..Our results suggest that geniposide pretreatment inhibits H/R-induced myocardial apoptosis by reversing mitochondrial dysfunction, an effect in part due to activation of GLP-1R and PI3K/AKT signaling pathway. ..
  5. Pao W, Girard N. New driver mutations in non-small-cell lung cancer. Lancet Oncol. 2011;12:175-80 pubmed publisher
    ..here, we discuss subsets defined by so-called driver mutations in ALK, HER2 (also known as ERBB2), BRAF, PIK3CA, AKT1, MAP2K1, and MET...
  6. Dominguez V, Raimondi C, Somanath S, Bugliani M, Loder M, Edling C, et al. Class II phosphoinositide 3-kinase regulates exocytosis of insulin granules in pancreatic beta cells. J Biol Chem. 2011;286:4216-25 pubmed publisher
    ..Our results reveal a critical role for PI3K-C2? in ? cells and suggest that down-regulation of PI3K-C2? may be a feature of type 2 diabetes. ..
  7. Zhang L, Yang N, Katsaros D, Huang W, Park J, Fracchioli S, et al. The oncogene phosphatidylinositol 3'-kinase catalytic subunit alpha promotes angiogenesis via vascular endothelial growth factor in ovarian carcinoma. Cancer Res. 2003;63:4225-31 pubmed
    ..Nat. Genet., 21: 99-102, 1999]. In this study, we examined the expression of PIK3CA mRNA and its p110alpha protein product in human ovarian carcinoma and investigated its role in regulating angiogenesis via vascular ..
  8. Hers I, Bell C, Poole A, Jiang D, Denton R, Schaefer E, et al. Reciprocal feedback regulation of insulin receptor and insulin receptor substrate tyrosine phosphorylation by phosphoinositide 3-kinase in primary adipocytes. Biochem J. 2002;368:875-84 pubmed
  9. Carpenter C, Duckworth B, Auger K, Cohen B, Schaffhausen B, Cantley L. Purification and characterization of phosphoinositide 3-kinase from rat liver. J Biol Chem. 1990;265:19704-11 pubmed
    ..Substitution of Mn2+ for Mg2+ results in only approximately 10% of the Mg2(+)-dependent activity. Physiological calcium concentrations have no effect on the enzyme activity. Phosphoinositide 3-kinase has a broad pH optimum around 7. ..
  10. Lindhurst M, Parker V, Payne F, Sapp J, Rudge S, Harris J, et al. Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA. Nat Genet. 2012;44:928-33 pubmed publisher
    ..His1047Leu in PIK3CA, the gene that encodes the p110α catalytic subunit of PI3K, only in affected cells...
  11. Vargiu P, De Abajo R, Garcia Ranea J, Valencia A, Santisteban P, Crespo P, et al. The small GTP-binding protein, Rhes, regulates signal transduction from G protein-coupled receptors. Oncogene. 2004;23:559-68 pubmed
    ..Overall, our results provide the initial insights into the role in signal transduction of this novel Ras family member. ..
  12. Kaplan Albuquerque N, Garat C, Desseva C, Jones P, Nemenoff R. Platelet-derived growth factor-BB-mediated activation of Akt suppresses smooth muscle-specific gene expression through inhibition of mitogen-activated protein kinase and redistribution of serum response factor. J Biol Chem. 2003;278:39830-8 pubmed
    ..This was associated with appearance of serum response factor in the cytoplasm. These data indicate that activation of p85/p110 alpha/Akt mediates suppression of SM gene expression by PDGF. ..
  13. Xiao H, Shi W, Liu S, Wang W, Zhang B, Zhang Y, et al. 1,25-Dihydroxyvitamin D(3) prevents puromycin aminonucleoside-induced apoptosis of glomerular podocytes by activating the phosphatidylinositol 3-kinase/Akt-signaling pathway. Am J Nephrol. 2009;30:34-43 pubmed publisher
    ..1,25(OH)(2)D(3) reduced the PAN-induced podocyte apoptosis and loss of nephrin in PAN nephropathy rat. The anti-apoptotic effects of 1,25(OH)(2)D(3 )on podocytes may be partly attributable to activation of a PI3K/Akt survival pathway. ..
  14. Nelson V, Jiang Y, Dickman K, Ballou L, Lin R. Adipose tissue insulin resistance due to loss of PI3K p110? leads to decreased energy expenditure and obesity. Am J Physiol Endocrinol Metab. 2014;306:E1205-16 pubmed publisher
  15. 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. ..
  16. Wang H, Yang S, Liang H, Li C. HBx protein promotes oval cell proliferation by up-regulation of cyclin D1 via activation of the MEK/ERK and PI3K/Akt pathways. Int J Mol Sci. 2014;15:3507-18 pubmed publisher
  17. Diering G, Numata Y, Fan S, Church J, Numata M. Endosomal acidification by Na+/H+ exchanger NHE5 regulates TrkA cell-surface targeting and NGF-induced PI3K signaling. Mol Biol Cell. 2013;24:3435-48 pubmed publisher
    ..These results collectively suggest that endosomal pH modulates trafficking of Trk-family receptor tyrosine kinases, neurotrophin signaling, and possibly neuronal differentiation. ..
  18. 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
    ..Thus, p110α represents a selective target for the prevention of neointima formation after vascular injury, whereas p110β and p110δ expression and activity do not play a significant role. ..
  19. Sanders H, Albitar M. Somatic mutations of signaling genes in non-small-cell lung cancer. Cancer Genet Cytogenet. 2010;203:7-15 pubmed publisher
  20. Wen F, He S, Sun C, Li T, Wu S. PIK3CA and PIK3CB expression and relationship with multidrug resistance in colorectal carcinoma. Int J Clin Exp Pathol. 2014;7:8295-303 pubmed
    ..Thus, this study aims to evaluate the association between PIK3CA and PIK3CB expression and the MDR gene in colorectal cancer (CRC) patients...
  21. Kuo C, Liang C, Lai C, Liang S. Involvement of heat shock protein (Hsp)90 beta but not Hsp90 alpha in antiapoptotic effect of CpG-B oligodeoxynucleotide. J Immunol. 2007;178:6100-8 pubmed
    ..This study thus reveals the involvement of Hsp90beta but not Hsp90alpha in CpG-B ODN-mediated antiapoptotic response and that Hsp90beta is distinct from Hsp90alpha in regulation of the cellular function of immune cells. ..
  22. 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
    ..Moreover, the activated insulin receptor phosphorylates p55PIK in Sf9 cells, and insulin stimulates p55PIK phosphorylation in CHOIR/p55PIK cells. The unique features of p55PIK suggest that it is important in receptor signaling. ..
  23. Lee T, Chang N, Lin S. Inhibition of infarction-induced sympathetic innervation with endothelin receptor antagonism via a PI3K/GSK-3β-dependent pathway. Lab Invest. 2017;97:243-255 pubmed publisher
    ..ETA receptor antagonism is a mediator to attenuate sympathetic hyperinnervation probably through restoration of PI3K/Akt/GSK-3β/ROS signaling pathway, a potential pharmacological target for arrhythmias after infarction. ..
  24. Parrales A, Lopez E, López Colomé A. Thrombin activation of PI3K/PDK1/Akt signaling promotes cyclin D1 upregulation and RPE cell proliferation. Biochim Biophys Acta. 2011;1813:1758-66 pubmed publisher
  25. Asechi H, Hatano E, Nitta T, Tada M, Iwaisako K, Tamaki N, et al. Resistance to cisplatin-induced apoptosis via PI3K-dependent survivin expression in a rat hepatoma cell line. Int J Oncol. 2010;37:89-96 pubmed
    ..LY294002 also attenuated survivin expression induced by CDDP. Our results indicate that survivin expression via PI3K contributes to resistance to CDDP-induced apoptosis in a rat hepatoma cell line...
  26. Bansal N, Yendluri V, Wenham R. The molecular biology of endometrial cancers and the implications for pathogenesis, classification, and targeted therapies. Cancer Control. 2009;16:8-13 pubmed
    ..Novel targeted agents, either alone or in combination with cytotoxic agents, may result in superior treatment for patients. ..
  27. Baki L, Shioi J, Wen P, Shao Z, Schwarzman A, Gama Sosa M, et al. PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations. EMBO J. 2004;23:2586-96 pubmed
    ..Our data raise the possibility that PS1 may prevent development of AD pathology by activating the PI3K/Akt signaling pathway. In contrast, FAD mutations may promote AD pathology by inhibiting this pathway. ..
  28. Barbieri C, Bangma C, Bjartell A, Catto J, Culig Z, Gronberg H, et al. The mutational landscape of prostate cancer. Eur Urol. 2013;64:567-76 pubmed publisher
  29. Beauséjour M, Noël D, Thibodeau S, Bouchard V, Harnois C, Beaulieu J, et al. Integrin/Fak/Src-mediated regulation of cell survival and anoikis in human intestinal epithelial crypt cells: selective engagement and roles of PI3-K isoform complexes. Apoptosis. 2012;17:566-78 pubmed publisher
  30. Ren X, Sato Y, Harada K, Sasaki M, Furubo S, Song J, et al. Activation of the PI3K/mTOR pathway is involved in cystic proliferation of cholangiocytes of the PCK rat. PLoS ONE. 2014;9:e87660 pubmed publisher
  31. Guo X, Rajput A, Rose R, Hauser J, Beko A, Kuropatwinski K, et al. Mutant PIK3CA-bearing colon cancer cells display increased metastasis in an orthotopic model. Cancer Res. 2007;67:5851-8 pubmed
    Mutations in the PIK3CA gene are common in human cancers, including colon cancer...
  32. Yu H, Zhang H, Zhao W, Guo L, Li X, Li Y, et al. Gypenoside Protects against Myocardial Ischemia-Reperfusion Injury by Inhibiting Cardiomyocytes Apoptosis via Inhibition of CHOP Pathway and Activation of PI3K/Akt Pathway In Vivo and In Vitro. Cell Physiol Biochem. 2016;39:123-36 pubmed publisher
    ..the current study showed the potential of GP to alleviate myocardial I/R injury and preliminarily uncovered the underling mechanism driving this treatment. ..
  33. Gavard J, Lambert M, Grosheva I, Marthiens V, Irinopoulou T, Riou J, et al. Lamellipodium extension and cadherin adhesion: two cell responses to cadherin activation relying on distinct signalling pathways. J Cell Sci. 2004;117:257-70 pubmed
    ..These results provide additional information on the mechanisms by which cadherin coordinates adhesion with dynamic changes in the cytoskeleton to control cell shape and intercellular junction organization. ..
  34. Cros N, Tkatchenko A, Pisani D, Leclerc L, Leger J, Marini J, et al. Analysis of altered gene expression in rat soleus muscle atrophied by disuse. J Cell Biochem. 2001;83:508-19 pubmed
    ..In addition, the cloning of novel cDNAs underlined the efficiency of the chosen technical approach and gave novel possibilities to further decipher the molecular mechanisms of muscle atrophy. ..