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Gene Review

Akt1  -  thymoma viral proto-oncogene 1

Mus musculus

Synonyms: AKT1 kinase, Akt, PKB, PKB alpha, PKB/Akt, ...
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Disease relevance of Akt1


Psychiatry related information on Akt1


High impact information on Akt1

  • Our observations show that intestinal polyposis is initiated by PTEN-deficient ISCs that undergo excessive proliferation driven by Akt activation and nuclear localization of beta-catenin [12].
  • Snails, Swiss, and serum: the solution for Rac 'n' Rho [13].
  • Nuclear exclusion of the forkhead transcription factor FOXO3a by protein kinase Akt contributes to cell survival [14].
  • Forced activation of mTOR through upstream regulator Akt also increased ABI in colon cancer cells [15].
  • Loner and ARF6, which also control the proper membrane localization of another small GTPase, Rac, are key components of a cellular apparatus required for myoblast fusion and muscle development [16].

Chemical compound and disease context of Akt1


Biological context of Akt1


Anatomical context of Akt1


Associations of Akt1 with chemical compounds


Physical interactions of Akt1

  • We have used a combination of 14-3-3 binding and recognition by an antibody to the phosphorylation consensus of the enzyme to identify and isolate one of the major substrates of Akt, which is also a 14-3-3 binding protein [35].
  • Treatment with LY294002 or introduction of dn-Akt severely diminished DNA binding of Runx2 and Runx2-dependent transcription, whereas forced expression of myrAkt enhanced them [36].
  • Tcl1 interacts physically with Akt, increases its kinase activity and facilitates its transport to the nucleus [37].
  • Mas oncogene signaling and transformation require the small GTP-binding protein Rac [38].
  • Interestingly, FKHRL1 co-immunoprecipitated with Akt in PC12 cells, indicating that these two proteins can associate in these cells [39].

Enzymatic interactions of Akt1

  • Constitutive activation of Akt phosphorylated and inhibited the transcription factor Foxo3a [40].
  • We show here that withdrawal of all survival factors from MK-PT cells is associated with a progressive increase in the activity of extracellular signal-regulated kinase-1 and -2 (ERK1/2) and a progressive decrease in phosphorylated Akt, a kinase critical to cell survival [41].
  • The serine/threonine protein kinase Akt (protein kinase B) phosphorylates endothelial cell nitric oxide synthase (eNOS) and enhances its ability to generate nitric oxide (NO) [42].
  • Although purified DNA-PK could phosphorylate a peptide derived from Akt that contains amino acid Ser-473, it could not phosphorylate full-length Akt2 [43].
  • However, GSK-3 is also inhibited when it is phosphorylated by Akt, a downstream target of phosphatidylinositol 3-kinase (PI3K) [44].

Regulatory relationships of Akt1

  • CD28-dependent activation of protein kinase B/Akt blocks Fas-mediated apoptosis by preventing death-inducing signaling complex assembly [45].
  • Overexpression of either p55alpha or p50alpha reduces levels of activated Akt [46].
  • We propose a novel mechanism in which Stat3 regulates apoptosis by inducing expression of distinct PI(3)K regulatory subunits to downregulate PI(3)K-Akt-mediated survival signalling [46].
  • Overexpression of Gab2 enhanced the phosphorylation state of Akt, but not of ERK [47].
  • In fact, Akt was constitutively activated in the absence of EGF in AD3 cells [19].

Other interactions of Akt1


Analytical, diagnostic and therapeutic context of Akt1

  • The intracellular localization of Tcl1 and Akt1 in mouse fibroblasts was investigated by immunofluorescence [51].
  • In a rabbit hind limb model of vascular insufficiency, intramuscular activation of Akt1 signaling promoted collateral and capillary vessel formation and an accompanying increase in limb perfusion [52].
  • Like Akt1, Akt3 is not required for the maintenance of normal carbohydrate metabolism but is essential for the attainment of normal organ size [53].
  • Isografts of either PDK1- or PKCalpha-expressing cells but not Akt1-expressing cells in syngeneic mice led to formation of poorly differentiated mammary carcinomas [54].
  • Western blot demonstrated increased expression of Akt1 (by fivefold, p<0.01) and p44 MAP kinase (by sixfold, p<0.01), and decreased activation of caspase-3 (by 30%, p<0.05) [55].


  1. Akt1 regulates pathological angiogenesis, vascular maturation and permeability in vivo. Chen, J., Somanath, P.R., Razorenova, O., Chen, W.S., Hay, N., Bornstein, P., Byzova, T.V. Nat. Med. (2005) [Pubmed]
  2. The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/- mice. Chen, M.L., Xu, P.Z., Peng, X.D., Chen, W.S., Guzman, G., Yang, X., Di Cristofano, A., Pandolfi, P.P., Hay, N. Genes Dev. (2006) [Pubmed]
  3. Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2. Peng, X.D., Xu, P.Z., Chen, M.L., Hahn-Windgassen, A., Skeen, J., Jacobs, J., Sundararajan, D., Chen, W.S., Crawford, S.E., Coleman, K.G., Hay, N. Genes Dev. (2003) [Pubmed]
  4. Akt1/protein kinase Balpha is critical for ischemic and VEGF-mediated angiogenesis. Ackah, E., Yu, J., Zoellner, S., Iwakiri, Y., Skurk, C., Shibata, R., Ouchi, N., Easton, R.M., Galasso, G., Birnbaum, M.J., Walsh, K., Sessa, W.C. J. Clin. Invest. (2005) [Pubmed]
  5. Loss of Akt1 leads to severe atherosclerosis and occlusive coronary artery disease. Fernández-Hernando, C., Ackah, E., Yu, J., Suárez, Y., Murata, T., Iwakiri, Y., Prendergast, J., Miao, R.Q., Birnbaum, M.J., Sessa, W.C. Cell Metab. (2007) [Pubmed]
  6. Akt1 governs breast cancer progression in vivo. Ju, X., Katiyar, S., Wang, C., Liu, M., Jiao, X., Li, S., Zhou, J., Turner, J., Lisanti, M.P., Russell, R.G., Mueller, S.C., Ojeifo, J., Chen, W.S., Hay, N., Pestell, R.G. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  7. Lithium antagonizes dopamine-dependent behaviors mediated by an AKT/glycogen synthase kinase 3 signaling cascade. Beaulieu, J.M., Sotnikova, T.D., Yao, W.D., Kockeritz, L., Woodgett, J.R., Gainetdinov, R.R., Caron, M.G. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  8. 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]
  9. Paradoxical striatal cellular signaling responses to psychostimulants in hyperactive mice. Beaulieu, J.M., Sotnikova, T.D., Gainetdinov, R.R., Caron, M.G. J. Biol. Chem. (2006) [Pubmed]
  10. Enhanced Akt signaling is an early pro-survival response that reflects N-methyl-D-aspartate receptor activation in Huntington's disease knock-in striatal cells. Gines, S., Ivanova, E., Seong, I.S., Saura, C.A., MacDonald, M.E. J. Biol. Chem. (2003) [Pubmed]
  11. Regulation of Akt and glycogen synthase kinase-3 beta phosphorylation by sodium valproate and lithium. De Sarno, P., Li, X., Jope, R.S. Neuropharmacology (2002) [Pubmed]
  12. PTEN-deficient intestinal stem cells initiate intestinal polyposis. He, X.C., Yin, T., Grindley, J.C., Tian, Q., Sato, T., Tao, W.A., Dirisina, R., Porter-Westpfahl, K.S., Hembree, M., Johnson, T., Wiedemann, L.M., Barrett, T.A., Hood, L., Wu, H., Li, L. Nat. Genet. (2007) [Pubmed]
  13. Snails, Swiss, and serum: the solution for Rac 'n' Rho. Ridley, A.J., Hall, A. Cell (2004) [Pubmed]
  14. IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a. Hu, M.C., Lee, D.F., Xia, W., Golfman, L.S., Ou-Yang, F., Yang, J.Y., Zou, Y., Bao, S., Hanada, N., Saso, H., Kobayashi, R., Hung, M.C. Cell (2004) [Pubmed]
  15. Colonic polyposis caused by mTOR-mediated chromosomal instability in Apc+/Delta716 Cdx2+/- compound mutant mice. Aoki, K., Tamai, Y., Horiike, S., Oshima, M., Taketo, M.M. Nat. Genet. (2003) [Pubmed]
  16. Control of myoblast fusion by a guanine nucleotide exchange factor, loner, and its effector ARF6. Chen, E.H., Pryce, B.A., Tzeng, J.A., Gonzalez, G.A., Olson, E.N. Cell (2003) [Pubmed]
  17. Differential roles of phosphoinositide-dependent protein kinase-1 and akt1 expression and phosphorylation in breast cancer cell resistance to Paclitaxel, Doxorubicin, and gemcitabine. Liang, K., Lu, Y., Li, X., Zeng, X., Glazer, R.I., Mills, G.B., Fan, Z. Mol. Pharmacol. (2006) [Pubmed]
  18. Combinatorial activities of Akt and B-Raf/Erk signaling in a mouse model of androgen-independent prostate cancer. Gao, H., Ouyang, X., Banach-Petrosky, W.A., Gerald, W.L., Shen, M.M., Abate-Shen, C. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  19. PTEN/Akt signaling through epidermal growth factor receptor is prerequisite for angiogenesis by hepatocellular carcinoma cells that is susceptible to inhibition by gefitinib. Ueda, S., Basaki, Y., Yoshie, M., Ogawa, K., Sakisaka, S., Kuwano, M., Ono, M. Cancer Res. (2006) [Pubmed]
  20. Microarray-assisted pathway analysis identifies mitogen-activated protein kinase signaling as a mediator of resistance to the green tea polyphenol epigallocatechin 3-gallate in her-2/neu-overexpressing breast cancer cells. Guo, S., Lu, J., Subramanian, A., Sonenshein, G.E. Cancer Res. (2006) [Pubmed]
  21. The in vitro and in vivo effects of 2-(4-morpholinyl)-8-phenyl-chromone (LY294002), a specific inhibitor of phosphatidylinositol 3'-kinase, in human colon cancer cells. Semba, S., Itoh, N., Ito, M., Harada, M., Yamakawa, M. Clin. Cancer Res. (2002) [Pubmed]
  22. Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene. Chen, W.S., Xu, P.Z., Gottlob, K., Chen, M.L., Sokol, K., Shiyanova, T., Roninson, I., Weng, W., Suzuki, R., Tobe, K., Kadowaki, T., Hay, N. Genes Dev. (2001) [Pubmed]
  23. Regulation of pancreatic beta-cell growth and survival by the serine/threonine protein kinase Akt1/PKBalpha. Tuttle, R.L., Gill, N.S., Pugh, W., Lee, J.P., Koeberlein, B., Furth, E.E., Polonsky, K.S., Naji, A., Birnbaum, M.J. Nat. Med. (2001) [Pubmed]
  24. Antiapoptotic role of PPARbeta in keratinocytes via transcriptional control of the Akt1 signaling pathway. Di-Poï, N., Tan, N.S., Michalik, L., Wahli, W., Desvergne, B. Mol. Cell (2002) [Pubmed]
  25. Insulin signaling through Akt/protein kinase B analyzed by small interfering RNA-mediated gene silencing. Jiang, Z.Y., Zhou, Q.L., Coleman, K.A., Chouinard, M., Boese, Q., Czech, M.P. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  26. Ultraviolet-induced phosphorylation of p70(S6K) at Thr(389) and Thr(421)/Ser(424) involves hydrogen peroxide and mammalian target of rapamycin but not Akt and atypical protein kinase C. Huang, C., Li, J., Ke, Q., Leonard, S.S., Jiang, B.H., Zhong, X.S., Costa, M., Castranova, V., Shi, X. Cancer Res. (2002) [Pubmed]
  27. Phosphoinositide-dependent kinase-2 is a distinct protein kinase enriched in a novel cytoskeletal fraction associated with adipocyte plasma membranes. Hresko, R.C., Murata, H., Mueckler, M. J. Biol. Chem. (2003) [Pubmed]
  28. SH2-containing inositol phosphatase 2 predominantly regulates Akt2, and not Akt1, phosphorylation at the plasma membrane in response to insulin in 3T3-L1 adipocytes. Sasaoka, T., Wada, T., Fukui, K., Murakami, S., Ishihara, H., Suzuki, R., Tobe, K., Kadowaki, T., Kobayashi, M. J. Biol. Chem. (2004) [Pubmed]
  29. Isoform-specific requirement for Akt1 in the developmental regulation of cellular metabolism during lactation. Boxer, R.B., Stairs, D.B., Dugan, K.D., Notarfrancesco, K.L., Portocarrero, C.P., Keister, B.A., Belka, G.K., Cho, H., Rathmell, J.C., Thompson, C.B., Birnbaum, M.J., Chodosh, L.A. Cell Metab. (2006) [Pubmed]
  30. Akt1 signaling regulates integrin activation, matrix recognition, and fibronectin assembly. Somanath, P.R., Kandel, E.S., Hay, N., Byzova, T.V. J. Biol. Chem. (2007) [Pubmed]
  31. Critical role of the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase-3 signaling pathway in recovery from anthrax lethal toxin-induced cell cycle arrest and MEK cleavage in macrophages. Ha, S.D., Ng, D., Pelech, S.L., Kim, S.O. J. Biol. Chem. (2007) [Pubmed]
  32. Heterogeneous nuclear ribonucleoprotein A1 regulates cyclin D1 and c-myc internal ribosome entry site function through Akt signaling. Jo, O.D., Martin, J., Bernath, A., Masri, J., Lichtenstein, A., Gera, J. J. Biol. Chem. (2008) [Pubmed]
  33. Akt-mediated phosphorylation of CDK2 regulates its dual role in cell cycle progression and apoptosis. Maddika, S., Ande, S.R., Wiechec, E., Hansen, L.L., Wesselborg, S., Los, M. J. Cell. Sci. (2008) [Pubmed]
  34. Use of Akt inhibitor and a drug-resistant mutant validates a critical role for protein kinase B/Akt in the insulin-dependent regulation of glucose and system A amino acid uptake. Green, C.J., Göransson, O., Kular, G.S., Leslie, N.R., Gray, A., Alessi, D.R., Sakamoto, K., Hundal, H.S. J. Biol. Chem. (2008) [Pubmed]
  35. Identification of a proline-rich Akt substrate as a 14-3-3 binding partner. Kovacina, K.S., Park, G.Y., Bae, S.S., Guzzetta, A.W., Schaefer, E., Birnbaum, M.J., Roth, R.A. J. Biol. Chem. (2003) [Pubmed]
  36. Runx2 induces osteoblast and chondrocyte differentiation and enhances their migration by coupling with PI3K-Akt signaling. Fujita, T., Azuma, Y., Fukuyama, R., Hattori, Y., Yoshida, C., Koida, M., Ogita, K., Komori, T. J. Cell Biol. (2004) [Pubmed]
  37. Targeting mature T cell leukemia: new understanding of molecular pathways. Pekarsky, Y., Hallas, C., Croce, C.M. American journal of pharmacogenomics : genomics-related research in drug development and clinical practice. (2003) [Pubmed]
  38. Mas oncogene signaling and transformation require the small GTP-binding protein Rac. Zohn, I.E., Symons, M., Chrzanowska-Wodnicka, M., Westwick, J.K., Der, C.J. Mol. Cell. Biol. (1998) [Pubmed]
  39. Insulin-like growth factor-1-induced phosphorylation of the forkhead family transcription factor FKHRL1 is mediated by Akt kinase in PC12 cells. Zheng, W.H., Kar, S., Quirion, R. J. Biol. Chem. (2000) [Pubmed]
  40. Constitutive activation of Akt by Flt3 internal tandem duplications is necessary for increased survival, proliferation, and myeloid transformation. Brandts, C.H., Sargin, B., Rode, M., Biermann, C., Lindtner, B., Schwäble, J., Buerger, H., Müller-Tidow, C., Choudhary, C., McMahon, M., Berdel, W.E., Serve, H. Cancer Res. (2005) [Pubmed]
  41. Inhibition of ligand-independent ERK1/2 activity in kidney proximal tubular cells deprived of soluble survival factors up-regulates Akt and prevents apoptosis. Sinha, D., Bannergee, S., Schwartz, J.H., Lieberthal, W., Levine, J.S. J. Biol. Chem. (2004) [Pubmed]
  42. Acute modulation of endothelial Akt/PKB activity alters nitric oxide-dependent vasomotor activity in vivo. Luo, Z., Fujio, Y., Kureishi, Y., Rudic, R.D., Daumerie, G., Fulton, D., Sessa, W.C., Walsh, K. J. Clin. Invest. (2000) [Pubmed]
  43. mTOR.RICTOR is the Ser473 kinase for Akt/protein kinase B in 3T3-L1 adipocytes. Hresko, R.C., Mueckler, M. J. Biol. Chem. (2005) [Pubmed]
  44. The B cell antigen receptor regulates the transcriptional activator beta-catenin via protein kinase C-mediated inhibition of glycogen synthase kinase-3. Christian, S.L., Sims, P.V., Gold, M.R. J. Immunol. (2002) [Pubmed]
  45. CD28-dependent activation of protein kinase B/Akt blocks Fas-mediated apoptosis by preventing death-inducing signaling complex assembly. Jones, R.G., Elford, A.R., Parsons, M.J., Wu, L., Krawczyk, C.M., Yeh, W.C., Hakem, R., Rottapel, R., Woodgett, J.R., Ohashi, P.S. J. Exp. Med. (2002) [Pubmed]
  46. Stat3-induced apoptosis requires a molecular switch in PI(3)K subunit composition. Abell, K., Bilancio, A., Clarkson, R.W., Tiffen, P.G., Altaparmakov, A.I., Burdon, T.G., Asano, T., Vanhaesebroeck, B., Watson, C.J. Nat. Cell Biol. (2005) [Pubmed]
  47. G-CSF-induced tyrosine phosphorylation of Gab2 is Lyn kinase dependent and associated with enhanced Akt and differentiative, not proliferative, responses. Zhu, Q.S., Robinson, L.J., Roginskaya, V., Corey, S.J. Blood (2004) [Pubmed]
  48. An essential role for Rho, Rac, and Cdc42 GTPases in cell cycle progression through G1. Olson, M.F., Ashworth, A., Hall, A. Science (1995) [Pubmed]
  49. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Cho, H., Mu, J., Kim, J.K., Thorvaldsen, J.L., Chu, Q., Crenshaw, E.B., Kaestner, K.H., Bartolomei, M.S., Shulman, G.I., Birnbaum, M.J. Science (2001) [Pubmed]
  50. Akt-dependent cytokine production in mast cells. Kitaura, J., Asai, K., Maeda-Yamamoto, M., Kawakami, Y., Kikkawa, U., Kawakami, T. J. Exp. Med. (2000) [Pubmed]
  51. Tcl1 enhances Akt kinase activity and mediates its nuclear translocation. Pekarsky, Y., Koval, A., Hallas, C., Bichi, R., Tresini, M., Malstrom, S., Russo, G., Tsichlis, P., Croce, C.M. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  52. Myogenic Akt signaling regulates blood vessel recruitment during myofiber growth. Takahashi, A., Kureishi, Y., Yang, J., Luo, Z., Guo, K., Mukhopadhyay, D., Ivashchenko, Y., Branellec, D., Walsh, K. Mol. Cell. Biol. (2002) [Pubmed]
  53. Role for Akt3/protein kinase Bgamma in attainment of normal brain size. Easton, R.M., Cho, H., Roovers, K., Shineman, D.W., Mizrahi, M., Forman, M.S., Lee, V.M., Szabolcs, M., de Jong, R., Oltersdorf, T., Ludwig, T., Efstratiadis, A., Birnbaum, M.J. Mol. Cell. Biol. (2005) [Pubmed]
  54. Transformation of mammary epithelial cells by 3-phosphoinositide-dependent protein kinase-1 (PDK1) is associated with the induction of protein kinase Calpha. Zeng, X., Xu, H., Glazer, R.I. Cancer Res. (2002) [Pubmed]
  55. Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice. Wang, Q., Brubaker, P.L. Diabetologia (2002) [Pubmed]
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