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Gene Review

PIK3CG  -  phosphatidylinositol-4,5-bisphosphate 3...

Homo sapiens

Synonyms: PI3-kinase subunit gamma, PI3CG, PI3K, PI3K-gamma, PI3Kgamma, ...
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Disease relevance of PIK3CG


Psychiatry related information on PIK3CG


High impact information on PIK3CG

  • A shared feature of signal transduction downstream of most receptors on immune cells, as in nonhematopoietic cell types, is the activation of phosphoinositide 3-kinase (PI3K) [9].
  • We emphasize the concept that PI3K and its products are components of complex networks of interacting proteins and second messengers, rather than simple links in linear signaling cascades [9].
  • Understanding how specificity is achieved in PI3K signaling is of particular significance because altered regulation of this pathway is observed in many disease states, including leukemia and lymphoma [9].
  • In the early steps of this process, PI-3 kinase-generated D3-phosphorylated phosphoinositides bind the Akt PH domain and induce the translocation of the kinase to the plasma membrane where it co-localizes with phosphoinositide-dependent kinase-1 [10].
  • Extracellular stimuli evoke changes in phosphorylation that influence eIF4F activity, especially through the phosphoinositide 3-kinase (PI3K) and Ras signaling pathways [11].

Chemical compound and disease context of PIK3CG


Biological context of PIK3CG


Anatomical context of PIK3CG

  • The data argue that PI3K activity plays a central role in multiple signal transduction pathways within the human neutrophil leading to distinct cell functions [17].
  • Finally, we demonstrate that CXCR3-targeting chemokines control T-cell migration via PTX-sensitive, phospholipase C pathways and phosphatidylinositol kinases other than class I PI3Kgamma [18].
  • Overexpression of a dominant-negative AKT or a dominant-negative PI3 kinase p85 subunit in THP-1 monocytes attenuated the PlGF-mediated phosphorylation of ERK-1/2, cytochemokine secretion, and chemotaxis [19].
  • In summary, these data show that in human eosinophils, Th2-derived cytokines differentially activate both PI3K and MAP kinase signal transduction pathways with distinct functional consequences showing complex regulation of eosinophil effector functions [20].
  • Critical roles of c-Kit tyrosine residues 567 and 719 in stem cell factor-induced chemotaxis: contribution of src family kinase and PI3-kinase on calcium mobilization and cell migration [21].

Associations of PIK3CG with chemical compounds


Physical interactions of PIK3CG

  • Here we present evidence that PI3K/Akt is required for heat shock proteins to stabilize HIF-1alpha [25].
  • Finally, in co-immunoprecipitation experiments, we showed that PI3K physically interacted with TRIF [26].
  • P2Y12 is known to couple to activation of PI3 kinase and inhibition of adenylate cyclase, but we showed that neither of these signalling events couples to regulation of shape change by this receptor [27].
  • Heat shock treatment also caused a rapid increase in HSF-1 DNA binding activity that was partially dependent on PI-3K activity, as both the PI-3K inhibitors attenuated this response [28].
  • We investigated the role of G protein-coupled phosphoinositide 3-kinase gamma (PI3Kgamma) in ATX-mediated tumor cell motility stimulation [29].

Enzymatic interactions of PIK3CG

  • In addition to autophosphorylation PI3Kgamma is able to catalyse transphosphorylation of the adapter protein p101 and the protein kinase MEK-1 [30].

Regulatory relationships of PIK3CG

  • On the other hand, specific inhibitors of phosphatidylinositol 3-kinase (PI3K) suppressed TGF-beta1-induced CTGF expression in a concentration-dependent manner [31].
  • In addition, activation of PI3K may play a complementary role in the induction of cell cycle-regulated genes in response to IL-4 [32].
  • The results suggest that novel PKCs and PI3K initiate the response but both conventional and atypical PKCs are required for the maintenance of the UDP-induced phosphorylation of ERK1/2 [33].
  • Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner [34].
  • Collectively, these data suggest that the Th1-driving cytokine IL-12 and proinflammatory cytokine TNF-alpha are differentially regulated by PI 3-K and ERK 1/2 pathways in human MDMs during mycobacterial infection [35].

Other interactions of PIK3CG

  • Together, the data indicate that continuous outside-in signaling via P2Y(12) and both PI3Kbeta and PI3Kgamma isoforms is required for perpetuated alpha(IIb)beta(3) activation and maintenance of a platelet aggregate [36].
  • Our study indicated that the HRG-beta1-activated MEK1-ERK pathway has no demonstrable role in the induction of cell aggregation, whereas HRG-beta1-activated PI3K is required for enhancing breast cancer cell aggregation [37].
  • Here, we show that the A(3) adenosine receptor agonist Cl-IB-MECA stimulates PI3K-dependent phosphorylation of Akt leading to the reduction of basal levels of ERK1/2 phosphorylation, which in turn inhibits cell proliferation [38].
  • Our results suggested that PI3-kinase/p38(MAPK)/CREB pathway contributed to the EGF activation of NF-IL6beta gene expression [39].
  • Interestingly, the expression of Deltap85 also leads to inhibition of the SDF-1-mediated chemotactic response, albeit to a much lesser extent than achieved with the KD-PI3Kgamma mutant, typically in the range of 20-40% inhibition [40].

Analytical, diagnostic and therapeutic context of PIK3CG


  1. Genomic structure of the PIK3CG gene on chromosome band 7q22 and evaluation as a candidate myeloid tumor suppressor. Kratz, C.P., Emerling, B.M., Bonifas, J., Wang, W., Green, E.D., Beau, M.M., Shannon, K.M. Blood (2002) [Pubmed]
  2. Down-regulation of PIK3CG, a catalytic subunit of phosphatidylinositol 3-OH kinase, by CpG hypermethylation in human colorectal carcinoma. Semba, S., Itoh, N., Ito, M., Youssef, E.M., Harada, M., Moriya, T., Kimura, W., Yamakawa, M. Clin. Cancer Res. (2002) [Pubmed]
  3. PtdIns5P activates the host cell PI3-kinase/Akt pathway during Shigella flexneri infection. Pendaries, C., Tronchère, H., Arbibe, L., Mounier, J., Gozani, O., Cantley, L., Fry, M.J., Gaits-Iacovoni, F., Sansonetti, P.J., Payrastre, B. EMBO J. (2006) [Pubmed]
  4. Involvement of PI3K/PKG/ERK1/2 signaling pathways in cortical neurons to trigger protection by cotreatment of acetyl-L-carnitine and alpha-lipoic acid against HNE-mediated oxidative stress and neurotoxicity: Implications for Alzheimer's disease. Mohmmad Abdul, H., Butterfield, D.A. Free Radic. Biol. Med. (2007) [Pubmed]
  5. Tumor suppressor PTEN affects tau phosphorylation: deficiency in the phosphatase activity of PTEN increases aggregation of an FTDP-17 mutant Tau. Zhang, X., Zhang, Y.W., Liu, S., Bulloj, A., Tong, G.G., Zhang, Z., Liao, F.F., Xu, H. Molecular neurodegeneration [electronic resource]. (2006) [Pubmed]
  6. 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]
  7. 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]
  8. 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]
  9. Phosphoinositide 3-kinase: diverse roles in immune cell activation. Deane, J.A., Fruman, D.A. Annu. Rev. Immunol. (2004) [Pubmed]
  10. AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation. Chan, T.O., Rittenhouse, S.E., Tsichlis, P.N. Annu. Rev. Biochem. (1999) [Pubmed]
  11. eIF4 initiation factors: effectors of mRNA recruitment to ribosomes and regulators of translation. Gingras, A.C., Raught, B., Sonenberg, N. Annu. Rev. Biochem. (1999) [Pubmed]
  12. The CXC chemokine stromal cell-derived factor activates a Gi-coupled phosphoinositide 3-kinase in T lymphocytes. Sotsios, Y., Whittaker, G.C., Westwick, J., Ward, S.G. J. Immunol. (1999) [Pubmed]
  13. Role of p38 MAPK in CYP2E1-dependent arachidonic acid toxicity. Wu, D., Cederbaum, A.I. J. Biol. Chem. (2003) [Pubmed]
  14. Phosphatidylinositol 3-kinase, not extracellular signal-regulated kinase, regulates activation of the antioxidant-responsive element in IMR-32 human neuroblastoma cells. Lee, J.M., Hanson, J.M., Chu, W.A., Johnson, J.A. J. Biol. Chem. (2001) [Pubmed]
  15. Quercetin inhibits Shc- and phosphatidylinositol 3-kinase-mediated c-Jun N-terminal kinase activation by angiotensin II in cultured rat aortic smooth muscle cells. Yoshizumi, M., Tsuchiya, K., Kirima, K., Kyaw, M., Suzaki, Y., Tamaki, T. Mol. Pharmacol. (2001) [Pubmed]
  16. Activation of MAP kinase by muscarinic cholinergic receptors induces cell proliferation and protein synthesis in human breast cancer cells. Jiménez, E., Montiel, M. J. Cell. Physiol. (2005) [Pubmed]
  17. Interleukin 8-stimulated phosphatidylinositol-3-kinase activity regulates the migration of human neutrophils independent of extracellular signal-regulated kinase and p38 mitogen-activated protein kinases. Knall, C., Worthen, G.S., Johnson, G.L. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  18. CXCR3-mediated chemotaxis of human T cells is regulated by a Gi- and phospholipase C-dependent pathway and not via activation of MEK/p44/p42 MAPK nor Akt/PI-3 kinase. Smit, M.J., Verdijk, P., van der Raaij-Helmer, E.M., Navis, M., Hensbergen, P.J., Leurs, R., Tensen, C.P. Blood (2003) [Pubmed]
  19. Mechanism of monocyte activation and expression of proinflammatory cytochemokines by placenta growth factor. Selvaraj, S.K., Giri, R.K., Perelman, N., Johnson, C., Malik, P., Kalra, V.K. Blood (2003) [Pubmed]
  20. Analysis of signal transduction pathways in human eosinophils activated by chemoattractants and the T-helper 2-derived cytokines interleukin-4 and interleukin-5. Coffer, P.J., Schweizer, R.C., Dubois, G.R., Maikoe, T., Lammers, J.W., Koenderman, L. Blood (1998) [Pubmed]
  21. Critical roles of c-Kit tyrosine residues 567 and 719 in stem cell factor-induced chemotaxis: contribution of src family kinase and PI3-kinase on calcium mobilization and cell migration. Ueda, S., Mizuki, M., Ikeda, H., Tsujimura, T., Matsumura, I., Nakano, K., Daino, H., Honda Zi, Z., Sonoyama, J., Shibayama, H., Sugahara, H., Machii, T., Kanakura, Y. Blood (2002) [Pubmed]
  22. Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Roux, P.P., Ballif, B.A., Anjum, R., Gygi, S.P., Blenis, J. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  23. A member of Forkhead family transcription factor, FKHRL1, is one of the downstream molecules of phosphatidylinositol 3-kinase-Akt activation pathway in erythropoietin signal transduction. Kashii, Y., Uchida, M., Kirito, K., Tanaka, M., Nishijima, K., Toshima, M., Ando, T., Koizumi, K., Endoh, T., Sawada, K., Momoi, M., Miura, Y., Ozawa, K., Komatsu, N. Blood (2000) [Pubmed]
  24. 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]
  25. PI3K/Akt is required for heat shock proteins to protect hypoxia-inducible factor 1alpha from pVHL-independent degradation. Zhou, J., Schmid, T., Frank, R., Brüne, B. J. Biol. Chem. (2004) [Pubmed]
  26. Inhibition of phosphoinositide 3-kinase enhances TRIF-dependent NF-kappa B activation and IFN-beta synthesis downstream of Toll-like receptor 3 and 4. Aksoy, E., Vanden Berghe, W., Detienne, S., Amraoui, Z., Fitzgerald, K.A., Haegeman, G., Goldman, M., Willems, F. Eur. J. Immunol. (2005) [Pubmed]
  27. Evidence that the purinergic receptor P2Y12 potentiates platelet shape change by a Rho kinase-dependent mechanism. Hardy, A.R., Hill, D.J., Poole, A.W. Platelets (2005) [Pubmed]
  28. Opposing actions of phosphatidylinositol 3-kinase and glycogen synthase kinase-3beta in the regulation of HSF-1 activity. Bijur, G.N., Jope, R.S. J. Neurochem. (2000) [Pubmed]
  29. Autotaxin promotes motility via G protein-coupled phosphoinositide 3-kinase gamma in human melanoma cells. Lee, H.Y., Bae, G.U., Jung, I.D., Lee, J.S., Kim, Y.K., Noh, S.H., Stracke, M.L., Park, C.G., Lee, H.W., Han, J.W. FEBS Lett. (2002) [Pubmed]
  30. Differential regulation of lipid and protein kinase activities of phosphoinositide 3-kinase gamma in vitro. Bondev, A., Rubio, I., Wetzker, R. Biol. Chem. (1999) [Pubmed]
  31. C-Jun-NH2-terminal kinase mediates expression of connective tissue growth factor induced by transforming growth factor-beta1 in human lung fibroblasts. Utsugi, M., Dobashi, K., Ishizuka, T., Masubuchi, K., Shimizu, Y., Nakazawa, T., Mori, M. Am. J. Respir. Cell Mol. Biol. (2003) [Pubmed]
  32. Induction of genes involved in cell cycle progression by interleukin-4. McDonald, C., Vanscoy, S., Hearing, P., Reich, N.C. J. Interferon Cytokine Res. (2004) [Pubmed]
  33. Differential signalling of purinoceptors in HeLa cells through the extracellular signal-regulated kinase and protein kinase C pathways. Muscella, A., Greco, S., Elia, M.G., Storelli, C., Marsigliante, S. J. Cell. Physiol. (2004) [Pubmed]
  34. Erythropoietin promotes endothelial progenitor cell proliferative and adhesive properties in a PI 3-kinase-dependent manner. George, J., Goldstein, E., Abashidze, A., Wexler, D., Hamed, S., Shmilovich, H., Deutsch, V., Miller, H., Keren, G., Roth, A. Cardiovasc. Res. (2005) [Pubmed]
  35. Differential regulation of interleukin-12 and tumour necrosis factor-alpha by phosphatidylinositol 3-kinase and ERK 1/2 pathways during Mycobacterium tuberculosis infection. Yang, C.S., Lee, J.S., Jung, S.B., Oh, J.H., Song, C.H., Kim, H.J., Park, J.K., Paik, T.H., Jo, E.K. Clin. Exp. Immunol. (2006) [Pubmed]
  36. 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]
  37. Heregulin beta1-activated phosphatidylinositol 3-kinase enhances aggregation of MCF-7 breast cancer cells independent of extracellular signal-regulated kinase. Tan, M., Grijalva, R., Yu, D. Cancer Res. (1999) [Pubmed]
  38. A3 adenosine receptor activation inhibits cell proliferation via phosphatidylinositol 3-kinase/Akt-dependent inhibition of the extracellular signal-regulated kinase 1/2 phosphorylation in A375 human melanoma cells. Merighi, S., Benini, A., Mirandola, P., Gessi, S., Varani, K., Leung, E., Maclennan, S., Borea, P.A. J. Biol. Chem. (2005) [Pubmed]
  39. Induction of human NF-IL6beta by epidermal growth factor is mediated through the p38 signaling pathway and cAMP response element-binding protein activation in A431 cells. Wang, J.M., Tseng, J.T., Chang, W.C. Mol. Biol. Cell (2005) [Pubmed]
  40. Optimal chemotactic responses of leukemic T cells to stromal cell-derived factor-1 requires the activation of both class IA and IB phosphoinositide 3-kinases. Curnock, A.P., Sotsios, Y., Wright, K.L., Ward, S.G. J. Immunol. (2003) [Pubmed]
  41. The phosphatidylinositol 3'-kinase pathway is a dominant growth factor-activated cell survival pathway in LNCaP human prostate carcinoma cells. Lin, J., Adam, R.M., Santiestevan, E., Freeman, M.R. Cancer Res. (1999) [Pubmed]
  42. Phosphatidylinositol 3-kinase controls human intestinal epithelial cell differentiation by promoting adherens junction assembly and p38 MAPK activation. Laprise, P., Chailler, P., Houde, M., Beaulieu, J.F., Boucher, M.J., Rivard, N. J. Biol. Chem. (2002) [Pubmed]
  43. Combination treatment significantly enhances the efficacy of antitumor therapy by preferentially targeting angiogenesis. Kumar, P., Benedict, R., Urzua, F., Fischbach, C., Mooney, D., Polverini, P. Lab. Invest. (2005) [Pubmed]
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