proto oncogene proteins c akt


Summary: Protein-serine-threonine kinases that contain PLECKSTRIN HOMOLOGY DOMAINS and are activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. They play a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.

Top Publications

  1. Zhao T, Le Francois B, Goss G, Ding K, Bradbury P, Dimitroulakos J. Lovastatin inhibits EGFR dimerization and AKT activation in squamous cell carcinoma cells: potential regulation by targeting rho proteins. Oncogene. 2010;29:4682-92 pubmed publisher
    ..In BR21, patients showed a trend for improvement in OS (HR: 0.69, P=0.098) and DSS (HR: 0.62, P=0.048), but there was no statin x treatment interaction effect (P=0.34 and P=0.51 for OS and DSS, respectively)...
  2. Fernandez J, Rezai Zadeh K, Obregon D, Tan J. EGCG functions through estrogen receptor-mediated activation of ADAM10 in the promotion of non-amyloidogenic processing of APP. FEBS Lett. 2010;584:4259-67 pubmed publisher
  3. Spinella F, Rosanò L, Del Duca M, Di Castro V, Nicotra M, Natali P, et al. Endothelin-1 inhibits prolyl hydroxylase domain 2 to activate hypoxia-inducible factor-1alpha in melanoma cells. PLoS ONE. 2010;5:e11241 pubmed publisher
    ..These results further indicate that targeting ET(B)R may represent a potential therapeutic treatment of melanoma by impairing HIF-1alpha stability. ..
  4. Boyan G, Williams L, Legl A, Herbert Z. Proliferative cell types in embryonic lineages of the central complex of the grasshopper Schistocerca gregaria. Cell Tissue Res. 2010;341:259-77 pubmed publisher
    ..We propose a model of the way that neuroblasts, ganglion mother cells and secondary progenitors together produce the large cell numbers found in central complex lineages. ..
  5. Dong Y, Li A, Wang J, Weber J, Michel L. Synthetic lethality through combined Notch-epidermal growth factor receptor pathway inhibition in basal-like breast cancer. Cancer Res. 2010;70:5465-74 pubmed publisher
    ..Thus, we show that Notch pathway activation contributes to resistance to EGFR inhibition, and provide a novel treatment strategy for BLBCs. ..
  6. Qin X, Cheng Y, Yu L. Potential protection of curcumin against intracellular amyloid beta-induced toxicity in cultured rat prefrontal cortical neurons. Neurosci Lett. 2010;480:21-4 pubmed publisher
    ..The results suggest that curcumin may play a protective effect in primary cultured rat prefrontal cortical neurons against iAbeta-induced cytotoxicity, and both AKT and caspase-3 are involved in the curcumin-induced protective effects. ..
  7. Kang H, Chang W, Hurley M, VIGNERY A, Wu D. Important roles of PI3Kgamma in osteoclastogenesis and bone homeostasis. Proc Natl Acad Sci U S A. 2010;107:12901-6 pubmed publisher
    ..Our study also suggests that inhibition of PI3Kgamma, which is being considered as a potential therapeutic strategy for treating chronic inflammatory disorders, may result in an increase in bone mass. ..
  8. Feldman B, Fedida Metula S, Nita J, Sekler I, Fishman D. Coupling of mitochondria to store-operated Ca(2+)-signaling sustains constitutive activation of protein kinase B/Akt and augments survival of malignant melanoma cells. Cell Calcium. 2010;47:525-37 pubmed publisher
  9. Ou H, Lee W, Lee S, Huang C, Chiu T, Tsai K, et al. Ellagic acid protects endothelial cells from oxidized low-density lipoprotein-induced apoptosis by modulating the PI3K/Akt/eNOS pathway. Toxicol Appl Pharmacol. 2010;248:134-43 pubmed publisher
    ..The inhibition of oxLDL-induced endothelial apoptosis by ellagic acid is due at least in part to its anti-oxidant activity and its ability to modulate the PI3K/Akt/eNOS signaling pathway. ..

More Information


  1. Yakovlev V, Rabender C, Sankala H, Gauter Fleckenstein B, Fleckenstein K, Batinic Haberle I, et al. Proteomic analysis of radiation-induced changes in rat lung: Modulation by the superoxide dismutase mimetic MnTE-2-PyP(5+). Int J Radiat Oncol Biol Phys. 2010;78:547-54 pubmed publisher
  2. Yang H, Wei J, Zhang H, Song W, Wei W, Zhang L, et al. Upregulation of Toll-like Receptor (TLR) expression and release of cytokines from mast cells by IL-12. Cell Physiol Biochem. 2010;26:337-46 pubmed publisher
  3. Hinkel R, Bock Marquette I, Hatzopoulos A, Hazopoulos A, Kupatt C. Thymosin beta4: a key factor for protective effects of eEPCs in acute and chronic ischemia. Ann N Y Acad Sci. 2010;1194:105-11 pubmed publisher
    ..Therapeutic neovascularization was absent when thymosin beta4 shRNA was introduced into eEPCs before application. In conclusion, eEPCs are capable of acute and chronic ischemia protection in a thymosin beta4 dependent manner. ..
  4. Shahrzad S, Lacombe K, Adamcic U, Minhas K, Coomber B. Sodium dichloroacetate (DCA) reduces apoptosis in colorectal tumor hypoxia. Cancer Lett. 2010;297:75-83 pubmed publisher
    ..Thus DCA is cytoprotective to some CRC cells under hypoxic conditions, highlighting the need for further investigation before DCA can be used as a reliable apoptosis-inducing agent in cancer therapy. ..
  5. McGregor N, Patel L, Craig M, Weidner S, Wang S, Pienta K. AT-101 (R-(-)-gossypol acetic acid) enhances the effectiveness of androgen deprivation therapy in the VCaP prostate cancer model. J Cell Biochem. 2010;110:1187-94 pubmed publisher
    ..These data suggest that combination therapy of AT-101 and ADT may further delay the onset of AI disease, resulting in prolonged progression-free survival of prostate cancer patients. ..
  6. Li X, Zhan X, Lu C, Liu X, Wang X. Mechanisms of hepatocyte growth factor-mediated signaling in differentiation of pancreatic ductal epithelial cells into insulin-producing cells. Biochem Biophys Res Commun. 2010;398:389-94 pubmed publisher
    ..These data suggest that HGF induces PDECs to differentiate into insulin-producing cells through the PI3K/AKT signaling pathway. ..
  7. Hafizi S, Gustafsson A, Oslakovic C, Idevall Hagren O, Tengholm A, Sperandio O, et al. Tensin2 reduces intracellular phosphatidylinositol 3,4,5-trisphosphate levels at the plasma membrane. Biochem Biophys Res Commun. 2010;399:396-401 pubmed publisher
    ..In summary, we provide evidence that Tensin2, in addition to regulating cytoskeletal dynamics, influences phosphoinositide-Akt signalling through its PTPase domain. ..
  8. Stretton C, Evans A, Hundal H. Cellular depletion of atypical PKC{lambda} is associated with enhanced insulin sensitivity and glucose uptake in L6 rat skeletal muscle cells. Am J Physiol Endocrinol Metab. 2010;299:E402-12 pubmed publisher
    ..Our findings indicate that aPKCs are likely to play an important role in restraining proximal insulin signaling events but appear dispensable with respect to insulin-stimulated glucose uptake in cultured L6 muscle cells. ..
  9. Wijesekara N, Krishnamurthy M, Bhattacharjee A, Suhail A, Sweeney G, Wheeler M. Adiponectin-induced ERK and Akt phosphorylation protects against pancreatic beta cell apoptosis and increases insulin gene expression and secretion. J Biol Chem. 2010;285:33623-31 pubmed publisher
    ..This study demonstrates a lack of AMPK involvement and implicates Akt and ERK in adiponectin signaling, leading to protection against apoptosis and stimulation of insulin gene expression and secretion in pancreatic beta cells. ..
  10. Guo P, Kai Q, Gao J, Lian Z, Wu C, Wu C, et al. Cordycepin prevents hyperlipidemia in hamsters fed a high-fat diet via activation of AMP-activated protein kinase. J Pharmacol Sci. 2010;113:395-403 pubmed
    ..These results indicate that cordycepin prevents hyperlipidemia via activation of AMPK. Experiments on abnormal metabolic mice indicated that cordycepin can also improve insulin sensitivity effectively. ..
  11. Fife M, Salmon N, Hocking P, Kaiser P. Fine mapping of the chicken salmonellosis resistance locus (SAL1). Anim Genet. 2009;40:871-7 pubmed publisher
    ..72, P = 0.00475). This region spans 14 genes, including two very striking functional candidates; CD27-binding protein (Siva) and the RAC-alpha serine/threonine protein kinase homolog, AKT1 (protein kinase B, PKB). ..
  12. Li X, Fan Z. The epidermal growth factor receptor antibody cetuximab induces autophagy in cancer cells by downregulating HIF-1alpha and Bcl-2 and activating the beclin 1/hVps34 complex. Cancer Res. 2010;70:5942-52 pubmed publisher
    ..Our findings suggest that the autophagy protects cancer cells from the proapoptotic effects of cetuximab. ..
  13. Murthy A, Defamie V, Smookler D, Di Grappa M, Horiuchi K, Federici M, et al. Ectodomain shedding of EGFR ligands and TNFR1 dictates hepatocyte apoptosis during fulminant hepatitis in mice. J Clin Invest. 2010;120:2731-44 pubmed publisher
  14. Protzek A, Rafacho A, Viscelli B, Bosqueiro J, Cappelli A, Paula F, et al. Insulin and glucose sensitivity, insulin secretion and beta-cell distribution in endocrine pancreas of the fruit bat Artibeus lituratus. Comp Biochem Physiol A Mol Integr Physiol. 2010;157:142-8 pubmed publisher
  15. You J, Park M, Song W, Lee Y. Dietary fish oil alleviates soleus atrophy during immobilization in association with Akt signaling to p70s6k and E3 ubiquitin ligases in rats. Appl Physiol Nutr Metab. 2010;35:310-8 pubmed publisher
  16. Fan C, Lu C, Yang J, Hu X, Ren Y, Cai H, et al. Signal pathway of GnRH-III inhibiting FSH-induced steroidogenesis in granulosa cells. Front Biosci (Elite Ed). 2010;2:1218-26 pubmed
    ..Therefore, it is suggested that GnRH-III inhibiting FSH-induced steroidogenenisis in GCs might be by suppressing FSH-induced its own receptor expression via NR5A2 and USF transcriptional factors. ..
  17. Chapuis N, Park S, Leotoing L, Tamburini J, Verdier F, Bardet V, et al. I?B kinase overcomes PI3K/Akt and ERK/MAPK to control FOXO3a activity in acute myeloid leukemia. Blood. 2010;116:4240-50 pubmed publisher
    ..The restoration of FOXO3a activity by interacting with its subcellular distribution may thus represent a new attractive therapeutic strategy for AML. ..
  18. Smolock E, Korshunov V. Pharmacological inhibition of Axl affects smooth muscle cell functions under oxidative stress. Vascul Pharmacol. 2010;53:185-92 pubmed publisher
    ..R428 and R572 decreased intracellular production of ROS in comparison to Fc-Axl. In conclusion, R428 and R572 are more potent inhibitors of ligand independent mediated Axl signaling compared to Fc-Axl in RASMs under oxidative stress. ..
  19. McKenzie J, Liu T, Goodson A, Grossman D. Survivin enhances motility of melanoma cells by supporting Akt activation and {alpha}5 integrin upregulation. Cancer Res. 2010;70:7927-37 pubmed publisher
    ..Together, our results showed that survivin enhanced the migration and invasion of melanocytic cells and suggested that survivin may promote melanoma metastasis by supporting Akt-dependent upregulation of ?5 integrin. ..
  20. Wei J, Nagy T, Vilgelm A, Zaika E, Ogden S, Romero Gallo J, et al. Regulation of p53 tumor suppressor by Helicobacter pylori in gastric epithelial cells. Gastroenterology. 2010;139:1333-43 pubmed publisher
    ..H pylori-induced dysregulation of p53 is a potential mechanism by which the microorganism increases the risk of gastric cancer in infected individuals. ..
  21. Li Y, Wang J, Santen R, Kim T, Park H, Fan P, et al. Estrogen stimulation of cell migration involves multiple signaling pathway interactions. Endocrinology. 2010;151:5146-56 pubmed publisher
    ..Each pathway represents a potential target for blocking cell migration and metastasis of breast cancer cells. ..
  22. Morishita A, Gong J, Nomura T, Yoshida H, Izuishi K, Suzuki Y, et al. The use of protein array to identify targetable receptor tyrosine kinases for treatment of human colon cancer. Int J Oncol. 2010;37:829-35 pubmed
    ..Therefore, the analysis of phospho-RTK expression by protein array as a useful tool might identify novel therapies for individual patients with colon cancer. ..
  23. Lin Y, Hung C, Tsai J, Lee J, Chen Y, Wei C, et al. Hispidulin potently inhibits human glioblastoma multiforme cells through activation of AMP-activated protein kinase (AMPK). J Agric Food Chem. 2010;58:9511-7 pubmed publisher
    ..On the basis of these results, we demonstrated that hispidulin has the potential to be a chemopreventive and therapeutic agent against human GBM. ..
  24. Kini V, Chavez A, Mehta D. A new role for PTEN in regulating transient receptor potential canonical channel 6-mediated Ca2+ entry, endothelial permeability, and angiogenesis. J Biol Chem. 2010;285:33082-91 pubmed publisher
    ..Ca(2+) entry through TRPC6 induces an increase in endothelial permeability and directly promotes angiogenesis. Thus, PTEN is indicated to play a role beyond suppressing PI3K signaling. ..
  25. Vaid M, Sharma S, Katiyar S. Honokiol, a phytochemical from the Magnolia plant, inhibits photocarcinogenesis by targeting UVB-induced inflammatory mediators and cell cycle regulators: development of topical formulation. Carcinogenesis. 2010;31:2004-11 pubmed publisher
    ..Together, our results indicate that honokiol holds promise for the prevention of UVB-induced skin cancer by targeting inflammatory mediators, cell cycle regulators and cell survival signals in UVB-exposed skin...
  26. Wang L, Jin Y, Arnoldussen Y, Jonson I, Qu S, Maelandsmo G, et al. STAMP1 is both a proliferative and an antiapoptotic factor in prostate cancer. Cancer Res. 2010;70:5818-28 pubmed publisher
    ..Taken together, these data suggest that STAMP1 is required for prostate cancer growth, which may be a useful target in prostate cancer treatment. ..
  27. Hixon M, Paccagnella L, Millham R, Perez Olle R, Gualberto A. Development of inhibitors of the IGF-IR/PI3K/Akt/mTOR pathway. Rev Recent Clin Trials. 2010;5:189-208 pubmed
  28. Fernandes M, Reddy M, Croteau N, Walz C, Weisbach H, Podar K, et al. Novel oncogenic mutations of CBL in human acute myeloid leukemia that activate growth and survival pathways depend on increased metabolism. J Biol Chem. 2010;285:32596-605 pubmed publisher
    ..Pathways that are activated by CBL gain-of-function mutations can be efficiently targeted by small molecule drugs. ..
  29. Shehata M, Schnabl S, Demirtas D, Hilgarth M, Hubmann R, Ponath E, et al. Reconstitution of PTEN activity by CK2 inhibitors and interference with the PI3-K/Akt cascade counteract the antiapoptotic effect of human stromal cells in chronic lymphocytic leukemia. Blood. 2010;116:2513-21 pubmed publisher
    ..In conclusion, bone marrow microenvironment modulates the PI3-K/Akt/PTEN cascade and prevents apoptosis of CLL cells. Combined inhibition of PI3-K/Akt and recovery of PTEN activity may represent a novel therapeutic concept for CLL. ..
  30. Krech T, Thiede M, Hilgenberg E, Schafer R, Jurchott K. Characterization of AKT independent effects of the synthetic AKT inhibitors SH-5 and SH-6 using an integrated approach combining transcriptomic profiling and signaling pathway perturbations. BMC Cancer. 2010;10:287 pubmed publisher
    ..The effects are mostly cell line specific and have an influence at the outcome of the treatment. In view of potential clinical trials it will be necessary to take these diverse effects into consideration to optimize patient treatment. ..
  31. Nam S, Seo H, Park H, An S, Kim J, Yang K, et al. Phosphorylation of CLK2 at serine 34 and threonine 127 by AKT controls cell survival after ionizing radiation. J Biol Chem. 2010;285:31157-63 pubmed publisher
    ..Our results suggest that AKT activation controls cell survival to ionizing radiation by phosphorylating CLK2, revealing an important regulatory mechanism required for promoting cell survival. ..
  32. Laguë M, Detmar J, Paquet M, Boyer A, Richards J, Adamson S, et al. Decidual PTEN expression is required for trophoblast invasion in the mouse. Am J Physiol Endocrinol Metab. 2010;299:E936-46 pubmed publisher
    ..Together, these data demonstrate novel roles of PTEN in the mammalian uterus and its requirement for proper trophoblast invasion and decidual regression. ..
  33. Yang E, Jiang J, Lee S, Yang S, Hwang H, Lee M, et al. Bee venom attenuates neuroinflammatory events and extends survival in amyotrophic lateral sclerosis models. J Neuroinflammation. 2010;7:69 pubmed publisher
    ..From these findings, our research suggests BV could be a potential therapeutic agent for anti-neuroinflammatory effects in an animal model of ALS. ..
  34. Becher O, Holland E. Evidence for and against regional differences in neural stem and progenitor cells of the CNS. Genes Dev. 2010;24:2233-8 pubmed publisher
    ..In this issue of Genes & Development, Lee and colleagues (pp. 2317-2329) examine how NF1 regulates NSC proliferation and glial differentiation in the brainstem and cortex of the postnatal mouse brain. ..
  35. Li Z, Jo J, Jia J, Lo S, Whitcomb D, Jiao S, et al. Caspase-3 activation via mitochondria is required for long-term depression and AMPA receptor internalization. Cell. 2010;141:859-71 pubmed publisher
    ..NMDA receptor stimulation that induces LTD transiently activates caspase-3 in dendrites, without causing cell death. These data indicate an unexpected causal link between the molecular mechanisms of apoptosis and LTD. ..
  36. Norman K, Sarnow P. Herpes Simplex Virus is Akt-ing in translational control. Genes Dev. 2010;24:2583-6 pubmed publisher
  37. Schwaiberger A, Heiss E, Cabaravdic M, Oberan T, Zaujec J, Schachner D, et al. Indirubin-3'-monoxime blocks vascular smooth muscle cell proliferation by inhibition of signal transducer and activator of transcription 3 signaling and reduces neointima formation in vivo. Arterioscler Thromb Vasc Biol. 2010;30:2475-81 pubmed publisher
  38. Kladney R, Cardiff R, Kwiatkowski D, Chiang G, Weber J, Arbeit J, et al. Tuberous sclerosis complex 1: an epithelial tumor suppressor essential to prevent spontaneous prostate cancer in aged mice. Cancer Res. 2010;70:8937-47 pubmed publisher
    ..1 prostatic epithelial knockout mice. Thus, TSC1 inactivation distal to PI3K and AKT activation is sufficient to activate a molecular signaling cascade producing prostatic neoplasia and focal carcinogenesis. ..
  39. Hu L, Sun Z, Wen Y, Cheng G, Wang S, Zhao H, et al. ATP-mediated protein kinase B Akt/mammalian target of rapamycin mTOR/p70 ribosomal S6 protein p70S6 kinase signaling pathway activation promotes improvement of locomotor function after spinal cord injury in rats. Neuroscience. 2010;169:1046-62 pubmed publisher
    ..We suggest that modulation of this protein kinase signaling pathway activity should be considered as a potential therapeutic strategy for SCI. ..
  40. Cervantes Villagrana A, García Román J, Gonzalez Espinosa C, Lamas M. Pharmacological inhibition of N-methyl d-aspartate receptor promotes secretion of vascular endothelial growth factor in müller cells: effects of hyperglycemia and hypoxia. Curr Eye Res. 2010;35:733-41 pubmed publisher
    ..We suggest that conditions present on diabetic retinopathy could cause malfunction of control points on VEGF synthesis on Müller cells. ..
  41. Mukherjee K, Peng D, Brifkani Z, Belkhiri A, Pera M, Koyama T, et al. Dopamine and cAMP regulated phosphoprotein MW 32 kDa is overexpressed in early stages of gastric tumorigenesis. Surgery. 2010;148:354-63 pubmed publisher
    ..The ability of DARPP-32 to transform NIH3T3 cells and to regulate AKT and BCL-2 underscores its possible oncogenic potential. ..
  42. Park S, Choi J. Inhibition of beta-catenin/Tcf signaling by flavonoids. J Cell Biochem. 2010;110:1376-85 pubmed publisher
  43. Lee H, Park S, Almazari I, Kim E, Na H, Surh Y. Piceatannol induces heme oxygenase-1 expression in human mammary epithelial cells through activation of ARE-driven Nrf2 signaling. Arch Biochem Biophys. 2010;501:142-50 pubmed publisher
    ..The characteristic catechol moiety of piceatannol appears to be critical for induction of Nrf2 activation and subsequent upregulation of HO-1. ..
  44. Ning K, Drepper C, Valori C, Ahsan M, Wyles M, Higginbottom A, et al. PTEN depletion rescues axonal growth defect and improves survival in SMN-deficient motor neurons. Hum Mol Genet. 2010;19:3159-68 pubmed publisher
    ..Taken together, these data indicate that PTEN-mediated regulation of protein synthesis in motor neurons could represent a target for therapy in spinal muscular atrophy. ..
  45. Pianta A, Puppin C, Franzoni A, Fabbro D, Di Loreto C, Bulotta S, et al. Nucleophosmin is overexpressed in thyroid tumors. Biochem Biophys Res Commun. 2010;397:499-504 pubmed publisher
    ..It seems as a result of a dysregulation occurring at protein and not transcriptional level related to an increase of p-Akt levels of transformed thyrocytes. ..
  46. Hsieh D, Hsieh A, Stea B, Ellsworth R. IGFBP2 promotes glioma tumor stem cell expansion and survival. Biochem Biophys Res Commun. 2010;397:367-72 pubmed publisher
    ..Given the current dearth of selective molecular targets against GSCs, we anticipate our results to be of high therapeutic relevance in combating the rapid and lethal course of GBM. ..
  47. Mohseni M, Park B. PIK3CA and KRAS mutations predict for response to everolimus therapy: now that's RAD001. J Clin Invest. 2010;120:2655-8 pubmed publisher
    ..These data suggest that mTOR inhibitors currently in use will be ineffective against cancers that have a mutation in either KRAS or BRAF despite having PI3K/AKT/mTOR pathway activation. ..
  48. Chang Z, Zhang Q, Feng Q, Xu J, Teng T, Luan Q, et al. Deletion of Akt1 causes heart defects and abnormal cardiomyocyte proliferation. Dev Biol. 2010;347:384-91 pubmed publisher
    ..Our study suggests that Akt1 is essential for heart development and function, in part, through suppression of p38MAPK activation...
  49. Gilot D, Giudicelli F, Lagadic Gossmann D, Fardel O. Akti-1/2, an allosteric inhibitor of Akt 1 and 2, efficiently inhibits CaMKI? activity and aryl hydrocarbon receptor pathway. Chem Biol Interact. 2010;188:546-52 pubmed publisher
    ..This may impact on the therapeutic application of Akti-1/2 and structurally-related compounds. ..
  50. Bar N, Dikstein R. miR-22 forms a regulatory loop in PTEN/AKT pathway and modulates signaling kinetics. PLoS ONE. 2010;5:e10859 pubmed publisher
    ..Our results suggest that miR-22 acts to fine-tune the dynamics of PTEN/AKT/FoxO1 pathway. ..
  51. Yamaguchi M, Suyari O, Nagai R, Takahashi M. dGirdin a new player of Akt /PKB signaling in Drosophila Melanogaster. Front Biosci (Landmark Ed). 2010;15:1164-71 pubmed
    ..Possible use of the Drosophila Girdin model in understanding the mechanisms of cancer progression and in developing preventive and therapeutic strategies will be discussed...
  52. Kobayashi H, Butler J, O Donnell R, Kobayashi M, Ding B, Bonner B, et al. Angiocrine factors from Akt-activated endothelial cells balance self-renewal and differentiation of haematopoietic stem cells. Nat Cell Biol. 2010;12:1046-56 pubmed publisher
  53. Chen X, Liu F, Song X, Wang Z, Dong Z, Hu Z, et al. Rapamycin regulates Akt and ERK phosphorylation through mTORC1 and mTORC2 signaling pathways. Mol Carcinog. 2010;49:603-10 pubmed publisher