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Gene Review

Pik3cg  -  phosphoinositide-3-kinase, catalytic,...

Mus musculus

Synonyms: 5830428L06Rik, PI(3)Kgamma, PI3-kinase subunit gamma, PI3K, PI3K-gamma, ...
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Disease relevance of Pik3cg


Psychiatry related information on Pik3cg


High impact information on Pik3cg


Chemical compound and disease context of Pik3cg


Biological context of Pik3cg


Anatomical context of Pik3cg


Associations of Pik3cg with chemical compounds

  • PI3Kgamma-derived PtdIns(3,4,5)P(3) was instrumental for initiating a sustained influx of external Ca(2+) and degranulation [9].
  • DOCK2 and PI3Kgamma thus play distinct roles during T and B cell integrin activation and migration [20].
  • Adenosine, acting through the A(3) adenosine receptor (A(3)AR) as well as other agonists of G(alphai)-coupled GPCRs, transiently increased PtdIns(3,4,5)P(3) exclusively via PI3Kgamma [9].
  • Protection from angiotensin II-mediated vasculotoxic and hypertensive response in mice lacking PI3Kgamma [18].
  • Gene-targeted mice were used to evaluate the role of the gamma isoform of phosphoinositide 3-kinase (PI3Kgamma) in dendritic cell (DC) migration and induction of specific T-cell-mediated immune responses [19].
  • Identical responses were observed when endogenous chemokine production was induced by TNFalpha; leukocyte emigration was reduced in PI3Kgamma(-/-) mice [21].

Physical interactions of Pik3cg

  • In vitro binding experiments revealed that the EphA8 juxtamembrane segment was sufficient for the formation of a stable complex with p110gamma [22].

Regulatory relationships of Pik3cg


Other interactions of Pik3cg

  • This effect was partially dependent on the PI3K subunits p85alpha and p110gamma [27].
  • In response to angiotensin II, PI3Kgamma was required for the activation of Rac and the subsequent triggering of ROS production [18].
  • Infusion with p110beta/p85alpha or p110gamma PI3K in the presence of PI(4,5)P2 also restored I(Ca,L) density to wild-type levels [28].
  • Cutting edge: T cell development requires the combined activities of the p110gamma and p110delta catalytic isoforms of phosphatidylinositol 3-kinase [29].
  • Among neutrophils that did accumulate in the lungs of the PI3-Kgamma(-/-) mice after endotoxin administration, activation of NF-kappaB and expression of proinflammatory cytokines was diminished compared with levels present in lung neutrophils from PI3-Kgamma(+/+) mice [30].
  • These observations identify p110delta as a key therapeutic target among PI3K isoforms for allergy- and mast cell-related diseases [31].

Analytical, diagnostic and therapeutic context of Pik3cg

  • We show that, in PI3KgammaKD/KD hearts, cAMP levels are normal and that PI3Kgamma-deficient mice but not PI3KgammaKD/KD mice develop dramatic myocardial damage after chronic pressure overload induced by transverse aortic constriction (TAC) [7].
  • These data indicate that PI3Kgamma is a key transducer of the intracellular signals that are evoked by angiotensin II and suggest that blocking PI3Kgamma function might be exploited to improve therapeutic intervention on hypertension [18].
  • Nevertheless, only microinjection of anti-p110alpha (and not p110gamma) antibody inhibited both insulin- and Q209L-Galphaq-induced GLUT4 translocation, suggesting that the metabolic effects induced by Q209L-Galphaq are dependent on the p110alpha subunit of PI3-kinase [32].
  • Using E13 mouse SMG organ cultures, we showed that inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase), wortmannin and LY294002, substantially inhibited branching morphogenesis in SMG [33].
  • Experiments with adoptive transfer of bone marrow showed that PI3Kgamma in eosinophils but not in non-bone marrow-derived cells was required for their accumulation [34].


  1. Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Camps, M., Rückle, T., Ji, H., Ardissone, V., Rintelen, F., Shaw, J., Ferrandi, C., Chabert, C., Gillieron, C., Françon, B., Martin, T., Gretener, D., Perrin, D., Leroy, D., Vitte, P.A., Hirsch, E., Wymann, M.P., Cirillo, R., Schwarz, M.K., Rommel, C. Nat. Med. (2005) [Pubmed]
  2. Regulation of myocardial contractility and cell size by distinct PI3K-PTEN signaling pathways. Crackower, M.A., Oudit, G.Y., Kozieradzki, I., Sarao, R., Sun, H., Sasaki, T., Hirsch, E., Suzuki, A., Shioi, T., Irie-Sasaki, J., Sah, R., Cheng, H.Y., Rybin, V.O., Lembo, G., Fratta, L., Oliveira-dos-Santos, A.J., Benovic, J.L., Kahn, C.R., Izumo, S., Steinberg, S.F., Wymann, M.P., Backx, P.H., Penninger, J.M. Cell (2002) [Pubmed]
  3. Colorectal carcinomas in mice lacking the catalytic subunit of PI(3)Kgamma. Sasaki, T., Irie-Sasaki, J., Horie, Y., Bachmaier, K., Fata, J.E., Li, M., Suzuki, A., Bouchard, D., Ho, A., Redston, M., Gallinger, S., Khokha, R., Mak, T.W., Hawkins, P.T., Stephens, L., Scherer, S.W., Tsao, M., Penninger, J.M. Nature (2000) [Pubmed]
  4. Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Hirsch, E., Katanaev, V.L., Garlanda, C., Azzolino, O., Pirola, L., Silengo, L., Sozzani, S., Mantovani, A., Altruda, F., Wymann, M.P. Science (2000) [Pubmed]
  5. PS1 activates PI3K thus inhibiting GSK-3 activity and tau overphosphorylation: effects of FAD mutations. Baki, L., Shioi, J., Wen, P., Shao, Z., Schwarzman, A., Gama-Sosa, M., Neve, R., Robakis, N.K. EMBO J. (2004) [Pubmed]
  6. 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]
  7. PI3Kgamma modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects. Patrucco, E., Notte, A., Barberis, L., Selvetella, G., Maffei, A., Brancaccio, M., Marengo, S., Russo, G., Azzolino, O., Rybalkin, S.D., Silengo, L., Altruda, F., Wetzker, R., Wymann, M.P., Lembo, G., Hirsch, E. Cell (2004) [Pubmed]
  8. Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease. Backman, S.A., Stambolic, V., Suzuki, A., Haight, J., Elia, A., Pretorius, J., Tsao, M.S., Shannon, P., Bolon, B., Ivy, G.O., Mak, T.W. Nat. Genet. (2001) [Pubmed]
  9. Phosphoinositide 3-kinase gamma is an essential amplifier of mast cell function. Laffargue, M., Calvez, R., Finan, P., Trifilieff, A., Barbier, M., Altruda, F., Hirsch, E., Wymann, M.P. Immunity (2002) [Pubmed]
  10. Ablation of phosphoinositide 3-kinase-gamma reduces the severity of acute pancreatitis. Lupia, E., Goffi, A., De Giuli, P., Azzolino, O., Bosco, O., Patrucco, E., Vivaldo, M.C., Ricca, M., Wymann, M.P., Hirsch, E., Montrucchio, G., Emanuelli, G. Am. J. Pathol. (2004) [Pubmed]
  11. Hyperinsulinemia, glucose intolerance, and dyslipidemia induced by acute inhibition of phosphoinositide 3-kinase signaling in the liver. Miyake, K., Ogawa, W., Matsumoto, M., Nakamura, T., Sakaue, H., Kasuga, M. J. Clin. Invest. (2002) [Pubmed]
  12. Dual modulation of cell survival and cell death by beta(2)-adrenergic signaling in adult mouse cardiac myocytes. Zhu, W.Z., Zheng, M., Koch, W.J., Lefkowitz, R.J., Kobilka, B.K., Xiao, R.P. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  13. 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]
  14. Roles of PLC-beta2 and -beta3 and PI3Kgamma in chemoattractant-mediated signal transduction. Li, Z., Jiang, H., Xie, W., Zhang, Z., Smrcka, A.V., Wu, D. Science (2000) [Pubmed]
  15. Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration. Sasaki, T., Irie-Sasaki, J., Jones, R.G., Oliveira-dos-Santos, A.J., Stanford, W.L., Bolon, B., Wakeham, A., Itie, A., Bouchard, D., Kozieradzki, I., Joza, N., Mak, T.W., Ohashi, P.S., Suzuki, A., Penninger, J.M. Science (2000) [Pubmed]
  16. Neutrophils lacking phosphoinositide 3-kinase gamma show loss of directionality during N-formyl-Met-Leu-Phe-induced chemotaxis. Hannigan, M., Zhan, L., Li, Z., Ai, Y., Wu, D., Huang, C.K. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  17. The relative role of PLCbeta and PI3Kgamma in platelet activation. Lian, L., Wang, Y., Draznin, J., Eslin, D., Bennett, J.S., Poncz, M., Wu, D., Abrams, C.S. Blood (2005) [Pubmed]
  18. Protection from angiotensin II-mediated vasculotoxic and hypertensive response in mice lacking PI3Kgamma. Vecchione, C., Patrucco, E., Marino, G., Barberis, L., Poulet, R., Aretini, A., Maffei, A., Gentile, M.T., Storto, M., Azzolino, O., Brancaccio, M., Colussi, G.L., Bettarini, U., Altruda, F., Silengo, L., Tarone, G., Wymann, M.P., Hirsch, E., Lembo, G. J. Exp. Med. (2005) [Pubmed]
  19. Defective dendritic cell migration and activation of adaptive immunity in PI3Kgamma-deficient mice. Del Prete, A., Vermi, W., Dander, E., Otero, K., Barberis, L., Luini, W., Bernasconi, S., Sironi, M., Santoro, A., Garlanda, C., Facchetti, F., Wymann, M.P., Vecchi, A., Hirsch, E., Mantovani, A., Sozzani, S. EMBO J. (2004) [Pubmed]
  20. Differential requirements for DOCK2 and phosphoinositide-3-kinase gamma during T and B lymphocyte homing. Nombela-Arrieta, C., Lacalle, R.A., Montoya, M.C., Kunisaki, Y., Megías, D., Marqués, M., Carrera, A.C., Mañes, S., Fukui, Y., Martínez-A, C., Stein, J.V. Immunity (2004) [Pubmed]
  21. Leukocyte PI3Kgamma and PI3Kdelta have temporally distinct roles for leukocyte recruitment in vivo. Liu, L., Puri, K.D., Penninger, J.M., Kubes, P. Blood (2007) [Pubmed]
  22. The EphA8 receptor regulates integrin activity through p110gamma phosphatidylinositol-3 kinase in a tyrosine kinase activity-independent manner. Gu, C., Park, S. Mol. Cell. Biol. (2001) [Pubmed]
  23. Phosphatidylinositol 3-kinase is involved in Toll-like receptor 4-mediated cytokine expression in mouse macrophages. Ojaniemi, M., Glumoff, V., Harju, K., Liljeroos, M., Vuori, K., Hallman, M. Eur. J. Immunol. (2003) [Pubmed]
  24. Resistance to thromboembolism in PI3Kgamma-deficient mice. Hirsch, E., Bosco, O., Tropel, P., Laffargue, M., Calvez, R., Altruda, F., Wymann, M., Montrucchio, G. FASEB J. (2001) [Pubmed]
  25. IL-1beta regulates expression of Cx32, occludin, and claudin-2 of rat hepatocytes via distinct signal transduction pathways. Yamamoto, T., Kojima, T., Murata, M., Takano, K., Go, M., Chiba, H., Sawada, N. Exp. Cell Res. (2004) [Pubmed]
  26. Haematopoietic colony stimulating factors CSF-1 and GM-CSF increase phosphatidylinositol 3-kinase activity in murine bone marrow-derived macrophages. Yusoff, P., Hamilton, J.A., Nolan, R.D., Phillips, W.A. Growth Factors (1994) [Pubmed]
  27. The PTEN/PI3K pathway governs normal vascular development and tumor angiogenesis. Hamada, K., Sasaki, T., Koni, P.A., Natsui, M., Kishimoto, H., Sasaki, J., Yajima, N., Horie, Y., Hasegawa, G., Naito, M., Miyazaki, J., Suda, T., Itoh, H., Nakao, K., Mak, T.W., Nakano, T., Suzuki, A. Genes Dev. (2005) [Pubmed]
  28. Galpha q inhibits cardiac L-type Ca2+ channels through phosphatidylinositol 3-kinase. Lu, Z., Jiang, Y.P., Ballou, L.M., Cohen, I.S., Lin, R.Z. J. Biol. Chem. (2005) [Pubmed]
  29. Cutting edge: T cell development requires the combined activities of the p110gamma and p110delta catalytic isoforms of phosphatidylinositol 3-kinase. Webb, L.M., Vigorito, E., Wymann, M.P., Hirsch, E., Turner, M. J. Immunol. (2005) [Pubmed]
  30. Involvement of phosphoinositide 3-kinases in neutrophil activation and the development of acute lung injury. Yum, H.K., Arcaroli, J., Kupfner, J., Shenkar, R., Penninger, J.M., Sasaki, T., Yang, K.Y., Park, J.S., Abraham, E. J. Immunol. (2001) [Pubmed]
  31. Isoform-specific functions of phosphoinositide 3-kinases: p110 delta but not p110 gamma promotes optimal allergic responses in vivo. Ali, K., Camps, M., Pearce, W.P., Ji, H., Rückle, T., Kuehn, N., Pasquali, C., Chabert, C., Rommel, C., Vanhaesebroeck, B. J. Immunol. (2008) [Pubmed]
  32. G alpha-q/11 protein plays a key role in insulin-induced glucose transport in 3T3-L1 adipocytes. Imamura, T., Vollenweider, P., Egawa, K., Clodi, M., Ishibashi, K., Nakashima, N., Ugi, S., Adams, J.W., Brown, J.H., Olefsky, J.M. Mol. Cell. Biol. (1999) [Pubmed]
  33. Role of PI 3-kinase and PIP3 in submandibular gland branching morphogenesis. Larsen, M., Hoffman, M.P., Sakai, T., Neibaur, J.C., Mitchell, J.M., Yamada, K.M. Dev. Biol. (2003) [Pubmed]
  34. Phosphoinositide-3 kinases critically regulate the recruitment and survival of eosinophils in vivo: importance for the resolution of allergic inflammation. Pinho, V., Souza, D.G., Barsante, M.M., Hamer, F.P., De Freitas, M.S., Rossi, A.G., Teixeira, M.M. J. Leukoc. Biol. (2005) [Pubmed]
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