The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Akt1  -  v-akt murine thymoma viral oncogene homolog 1

Rattus norvegicus

Synonyms: PKB, PKB alpha, Protein kinase B, Protein kinase B alpha, RAC-PK-alpha, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Akt1


Psychiatry related information on Akt1


High impact information on Akt1

  • Here we show that the serine/threonine protein kinase Akt (protein kinase B) can directly phosphorylate eNOS on serine 1179 and activate the enzyme, leading to NO production, whereas mutant eNOS (S1179A) is resistant to phosphorylation and activation by Akt [7].
  • Calcium promotes cell survival through CaM-K kinase activation of the protein-kinase-B pathway [8].
  • These results identify a Ca2+-triggered signalling cascade in which CaM-KK activates PKB, which in turn phosphorylates BAD and protects cells from apoptosis [8].
  • Here we report that Ca2+/calmodulin-dependent protein kinase kinase (CaM-KK) activates PKB directly, resulting in phosphorylation of BAD on serine residue 136 and the interaction of BAD with protein 14-3-3 [8].
  • The effect of NMDA on cell survival was blocked by transfection with dominant-negative forms of CaM-KK or PKB [8].

Chemical compound and disease context of Akt1


Biological context of Akt1

  • The agonists appeared to potentiate Akt1 phosphorylation in muscle and liver and both Akt1 and Akt2 in adipose [13].
  • Activation of Akt1 is necessary and sufficient to prevent apoptotic EC destruction, since inhibition of the phosphatidylinositide-3-kinase pathway as well as transfection of ECs with a dominant-negative Akt1 mutant abrogates vascular protection [2].
  • Protein kinase B (Akt1), a serine-threonine kinase closely involved in cell growth and survival, offers a strong potential to address both intrinsic and extrinsic mechanisms of neuronal injury [14].
  • Transfection of SH-SY5Y cells with a plasmid encoding a kinase-deficient dominant-negative Akt1 eliminates cytoprotection, suggesting that activation of Akt1 is necessary and sufficient to prevent apoptotic destruction [14].
  • Protein Kinase Balpha(PKBalpha, or Akt1) is believed to play a crucial role in programmed cell death, cancer progression and the insulin-signaling cascade [15].

Anatomical context of Akt1

  • Akt1 and Akt2 activations by insulin have a similar time course and are maximal by 2.5 min in adipocytes of both lean and obese rats [16].
  • In obese rats, insulin-stimulated Akt1 activity decreased 30% in muscle and 21% in adipose tissue but increased 37% in liver compared with lean littermates [16].
  • Akt1 provides a novel capacity to foster EC survival through the prevention of cysteine protease degradation of Bcl-x(L) that is intimately linked to the specific inhibition of caspase 1-, 3-, and 9-like activities and the modulation of mitochondrial membrane potential and cytochrome c release [2].
  • The goal of this study was to evaluate changes in the abundance and phosphorylation of Akt1 and Akt2 as potential mechanisms for enhanced insulin action after 20 days of moderate calorie restriction [CR; 60% of ad libitum (AL) intake] in rat skeletal muscle [17].
  • Saline or a replication defective adenoviral vector expressing constitutively-active Akt1 (myrAkt) or beta-galactosidase (betagal) was delivered to the myocardium of 8 week old rats one day prior to initiating doxorubicin administration [18].

Associations of Akt1 with chemical compounds

  • Maximal insulin-stimulated (100 nmol/l) glucose transport was reduced 70% in isolated adipocytes, with a rightward shift in the insulin dose response for transport and for Akt1 stimulation but normal sensitivity for Akt2 [16].
  • Further studies indicated that LY294002, an inhibitor of phosphoinositide 3-kinase that is an upstream signaling protein of Akt1, could block neuroprotection of preconditioning, and KN62, an inhibitor of calmodulin-dependent protein kinase, also achieved the same effects as LY294002 [1].
  • Therefore, both phosphoinositide 3-kinase and calmodulin-dependent protein kinase are involved in the activation of Akt1 in ischemic tolerance [1].
  • Insulin increased Akt1 activity 3.9-fold in glycerol-infused rats, and this was impaired 41% in lipid-infused rats [19].
  • Critical role for Akt1 in the modulation of apoptotic phosphatidylserine exposure and microglial activation [14].

Physical interactions of Akt1

  • Akt1 binding to JIP-1 acts as a regulatory gate preventing JNK activation, which is opened under conditions ischemia injury [5].
  • Furthermore, the results are consistent with a role for assembly of active eIF4G.eIF4E complex and activation of S6K1 in mediating the stimulation of mRNA translation initiation by IGF-I through a PKB/mTOR signaling pathway [20].

Enzymatic interactions of Akt1


Co-localisations of Akt1

  • Furthermore, PI3K also co-localized with p-PKB to the same site in the epithelium as determined by fluorescence microscopy, consistent with their localization at the ES [26].

Regulatory relationships of Akt1


Other interactions of Akt1


Analytical, diagnostic and therapeutic context of Akt1

  • Here we examined whether ischemic preconditioning down-regulates activation of the mixed lineage kinase-JNK signaling pathway via NMDA receptor-mediated Akt1 activation [1].
  • We also noted that pretreatment of LY294002 before preconditioning reversed both the inhibition of MLK3 activation at 6 h of reperfusion and the increase in Akt1 activation at 10 min of reperfusion [3].
  • PKB alpha/Akt1 was isolated by immunoprecipitation and 2D-gel electrophoresis, subjected to in-gel tryptic digestion, and cysteinyl nitrosothiols were reacted with iodoacetic acids [2-C(12)/C(13) = 50/50] under ascorbate reduction conditions [15].
  • The enhanced green fluorescent protein-tagged pleckstrin homology (PH) domain of protein kinase B, which selectively binds to phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 3,4,5-triphosphate, was translocated to the plasma membrane after treatment with either EGF or NGF [36].
  • Therefore, in this study we have investigated whether adenosine receptors (A(1), A(2A) and A(3)) activate PKB by Western blotting and determined the involvement of phosphatidylinositol 3-kinase (PI-3K)/PKB in adenosine-induced preconditioning in cultured newborn rat cardiomyocytes [10].


  1. Neuroprotective effects of preconditioning ischemia on ischemic brain injury through down-regulating activation of JNK1/2 via N-methyl-D-aspartate receptor-mediated Akt1 activation. Miao, B., Yin, X.H., Pei, D.S., Zhang, Q.G., Zhang, G.Y. J. Biol. Chem. (2005) [Pubmed]
  2. AKT1 drives endothelial cell membrane asymmetry and microglial activation through Bcl-xL and caspase 1, 3, and 9. Chong, Z.Z., Kang, J.Q., Maiese, K. Exp. Cell Res. (2004) [Pubmed]
  3. Neuroprotective effects of preconditioning ischaemia on ischaemic brain injury through inhibition of mixed-lineage kinase 3 via NMDA receptor-mediated Akt1 activation. Yin, X.H., Zhang, Q.G., Miao, B., Zhang, G.Y. J. Neurochem. (2005) [Pubmed]
  4. Akt promotes increased mammalian cell size by stimulating protein synthesis and inhibiting protein degradation. Faridi, J., Fawcett, J., Wang, L., Roth, R.A. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  5. Involvement of oxidative stress in the rapid Akt1 regulating a JNK scaffold during ischemia in rat hippocampus. Pan, J., Pei, D.S., Yin, X.H., Hui, L., Zhang, G.Y. Neurosci. Lett. (2006) [Pubmed]
  6. Activation of protein kinase B (Akt) signaling after electroconvulsive shock in the rat hippocampus. Kang, U.G., Roh, M.S., Jung, J.R., Shin, S.Y., Lee, Y.H., Park, J.B., Kim, Y.S. Prog. Neuropsychopharmacol. Biol. Psychiatry (2004) [Pubmed]
  7. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Fulton, D., Gratton, J.P., McCabe, T.J., Fontana, J., Fujio, Y., Walsh, K., Franke, T.F., Papapetropoulos, A., Sessa, W.C. Nature (1999) [Pubmed]
  8. Calcium promotes cell survival through CaM-K kinase activation of the protein-kinase-B pathway. Yano, S., Tokumitsu, H., Soderling, T.R. Nature (1998) [Pubmed]
  9. Resveratrol suppresses angiotensin II-induced Akt/protein kinase B and p70 S6 kinase phosphorylation and subsequent hypertrophy in rat aortic smooth muscle cells. Haider, U.G., Sorescu, D., Griendling, K.K., Vollmar, A.M., Dirsch, V.M. Mol. Pharmacol. (2002) [Pubmed]
  10. Activation of protein kinase B by adenosine A1 and A3 receptors in newborn rat cardiomyocytes. Germack, R., Griffin, M., Dickenson, J.M. J. Mol. Cell. Cardiol. (2004) [Pubmed]
  11. The neuroprotection of insulin on ischemic brain injury in rat hippocampus through negative regulation of JNK signaling pathway by PI3K/Akt activation. Hui, L., Pei, D.S., Zhang, Q.G., Guan, Q.H., Zhang, G.Y. Brain Res. (2005) [Pubmed]
  12. A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification. Pallafacchina, G., Calabria, E., Serrano, A.L., Kalhovde, J.M., Schiaffino, S. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  13. Potentiation of insulin signaling in tissues of Zucker obese rats after acute and long-term treatment with PPARgamma agonists. Jiang, G., Dallas-Yang, Q., Li, Z., Szalkowski, D., Liu, F., Shen, X., Wu, M., Zhou, G., Doebber, T., Berger, J., Moller, D.E., Zhang, B.B. Diabetes (2002) [Pubmed]
  14. Critical role for Akt1 in the modulation of apoptotic phosphatidylserine exposure and microglial activation. Kang, J.Q., Chong, Z.Z., Maiese, K. Mol. Pharmacol. (2003) [Pubmed]
  15. Site-specific detection of S-nitrosylated PKB alpha/Akt1 from rat soleus muscle using CapLC-Q-TOF(micro) mass spectrometry. Lu, X.M., Lu, M., Tompkins, R.G., Fischman, A.J. Journal of mass spectrometry : JMS. (2005) [Pubmed]
  16. Divergent regulation of Akt1 and Akt2 isoforms in insulin target tissues of obese Zucker rats. Kim, Y.B., Peroni, O.D., Franke, T.F., Kahn, B.B. Diabetes (2000) [Pubmed]
  17. Brief calorie restriction increases Akt2 phosphorylation in insulin-stimulated rat skeletal muscle. McCurdy, C.E., Davidson, R.T., Cartee, G.D. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  18. Elevated myocardial Akt signaling ameliorates doxorubicin-induced congestive heart failure and promotes heart growth. Taniyama, Y., Walsh, K. J. Mol. Cell. Cardiol. (2002) [Pubmed]
  19. Fatty acid infusion selectively impairs insulin action on Akt1 and protein kinase C lambda /zeta but not on glycogen synthase kinase-3. Kim, Y.B., Shulman, G.I., Kahn, B.B. J. Biol. Chem. (2002) [Pubmed]
  20. IGF-I activates the eIF4F system in cardiac muscle in vivo. Vary, T.C., Lang, C.H. Mol. Cell. Biochem. (2005) [Pubmed]
  21. Control of Ser2448 phosphorylation in the mammalian target of rapamycin by insulin and skeletal muscle load. Reynolds, T.H., Bodine, S.C., Lawrence, J.C. J. Biol. Chem. (2002) [Pubmed]
  22. Tobacco cembranoids protect the function of acute hippocampal slices against NMDA by a mechanism mediated by alpha4beta2 nicotinic receptors. Ferchmin, P.A., Hao, J., Perez, D., Penzo, M., Maldonado, H.M., Gonzalez, M.T., Rodriguez, A.D., de Vellis, J. J. Neurosci. Res. (2005) [Pubmed]
  23. Insulin-induced phosphorylation and activation of phosphodiesterase 3B in rat adipocytes: possible role for protein kinase B but not mitogen-activated protein kinase or p70 S6 kinase. Wijkander, J., Landström, T.R., Manganiello, V., Belfrage, P., Degerman, E. Endocrinology (1998) [Pubmed]
  24. The identification of ATP-citrate lyase as a protein kinase B (Akt) substrate in primary adipocytes. Berwick, D.C., Hers, I., Heesom, K.J., Moule, S.K., Tavare, J.M. J. Biol. Chem. (2002) [Pubmed]
  25. Diazoxide attenuates insulin secretion and hepatic lipogenesis in zucker diabetic fatty rats. Alemzadeh, R., Tushaus, K. Med. Sci. Monit. (2005) [Pubmed]
  26. Sertoli-germ cell anchoring junction dynamics in the testis are regulated by an interplay of lipid and protein kinases. Siu, M.K., Wong, C.H., Lee, W.M., Cheng, C.Y. J. Biol. Chem. (2005) [Pubmed]
  27. K-Ras-mediated increase in cyclooxygenase 2 mRNA stability involves activation of the protein kinase B1. Sheng, H., Shao, J., Dubois, R.N. Cancer Res. (2001) [Pubmed]
  28. Role of phospholipase C-gamma1 in insulin-like growth factor I-induced muscle differentiation of H9c2 cardiac myoblasts. Hong, F., Moon Ka, n.u.l.l., Kim, S.S., Kim, Y.S., Choi, Y.K., Bae, Y.S., Suh, P.G., Ryu, S.H., Choi, E.J., Ha, J., Kim, S.S. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  29. Insulin increases the association of Akt-2 with Glut4-containing vesicles. Calera, M.R., Martinez, C., Liu, H., Jack, A.K., Birnbaum, M.J., Pilch, P.F. J. Biol. Chem. (1998) [Pubmed]
  30. Integrative mitogenic role of protein kinase B/Akt in beta-cells. Trümper, K., Trümper, A., Trusheim, H., Arnold, R., Göke, B., Hörsch, D. Ann. N. Y. Acad. Sci. (2000) [Pubmed]
  31. The role of protein kinase B and mitogen-activated protein kinase in epidermal growth factor and tumor necrosis factor alpha-mediated rat hepatocyte survival and apoptosis. Roberts, R.A., James, N.H., Cosulich, S.C. Hepatology (2000) [Pubmed]
  32. Involvement of protein kinase B and mitogen-activated protein kinases in experimental normothermic liver ischaemia-reperfusion injury. Cursio, R., Filippa, N., Miele, C., Van Obberghen, E., Gugenheim, J. The British journal of surgery. (2006) [Pubmed]
  33. pERK, pAkt and pBad: A Possible Role in Cell Proliferation and Sustained Cellular Survival During Tumorigenesis and Tumor Progression in ENU Induced Transplacental Glioma Rat Model. Bhaskara, V.K., Sundaram, C., Babu, P.P. Neurochem. Res. (2006) [Pubmed]
  34. Sodium ferulate prevents amyloid-beta-induced neurotoxicity through suppression of p38 MAPK and upregulation of ERK-1/2 and Akt/protein kinase B in rat hippocampus. Jin, Y., Yan, E.Z., Fan, Y., Zong, Z.H., Qi, Z.M., Li, Z. Acta Pharmacol. Sin. (2005) [Pubmed]
  35. FSH activates phosphatidylinositol 3-kinase/protein kinase B signaling pathway in 20-day-old Sertoli cells independently of IGF-I. Meroni, S.B., Riera, M.F., Pellizzari, E.H., Galardo, M.N., Cigorraga, S.B. J. Endocrinol. (2004) [Pubmed]
  36. Two distinct regulatory mechanisms of neurotransmitter release by phosphatidylinositol 3-kinase. Itakura, M., Yamamori, S., Kuwahara, R., Sekiguchi, M., Takahashi, M. J. Neurochem. (2005) [Pubmed]
WikiGenes - Universities