AKT3

Summary

Gene Symbol: AKT3
Description: AKT serine/threonine kinase 3
Alias: MPPH, MPPH2, PKB-GAMMA, PKBG, PRKBG, RAC-PK-gamma, RAC-gamma, STK-2, RAC-gamma serine/threonine-protein kinase, PKB gamma, RAC-gamma serine/threonine protein kinase, v-akt murine thymoma viral oncogene homolog 3 (protein kinase B, gamma)
Species: human
Products:     AKT3

Top Publications

  1. Masure S, Haefner B, Wesselink J, Hoefnagel E, Mortier E, Verhasselt P, et al. Molecular cloning, expression and characterization of the human serine/threonine kinase Akt-3. Eur J Biochem. 1999;265:353-60 pubmed
    ..These observations suggest that Akt-3 is a promising target for the discovery of novel chemotherapeutic agents which do not interfere with insulin signalling. ..
  2. Boland E, Clayton Smith J, Woo V, McKee S, Manson F, Medne L, et al. Mapping of deletion and translocation breakpoints in 1q44 implicates the serine/threonine kinase AKT3 in postnatal microcephaly and agenesis of the corpus callosum. Am J Hum Genet. 2007;81:292-303 pubmed
    ..patient with postnatal MIC and ACC demonstrated a breakpoint within this region that is situated 20 kb upstream of AKT3, a serine-threonine kinase...
  3. Peng F, Dhillon N, Callen S, Yao H, Bokhari S, Zhu X, et al. Platelet-derived growth factor protects neurons against gp120-mediated toxicity. J Neurovirol. 2008;14:62-72 pubmed publisher
    ..Taken together these findings lead us to suggest that PDGF-BB could be considered as a therapeutic agent that can mitigate gp120-mediated neurotoxicity in HAD. ..
  4. Cheney L, Hou J, Morrison S, Pessin J, Steigbigel R. Nef inhibits glucose uptake in adipocytes and contributes to insulin resistance in human immunodeficiency virus type I infection. J Infect Dis. 2011;203:1824-31 pubmed publisher
    ..We have identified HIV Nef, which is detectable and antigenic in serum samples from HIV-infected people, as a novel contributor to the development of insulin resistance. ..
  5. Zhu X, Zhou F, Qin D, Zeng Y, Lv Z, Yao S, et al. Human immunodeficiency virus type 1 induces lytic cycle replication of Kaposi's-sarcoma-associated herpesvirus: role of Ras/c-Raf/MEK1/2, PI3K/AKT, and NF-?B signaling pathways. J Mol Biol. 2011;410:1035-51 pubmed publisher
  6. Poduri A, Evrony G, Cai X, Elhosary P, Beroukhim R, Lehtinen M, et al. Somatic activation of AKT3 causes hemispheric developmental brain malformations. Neuron. 2012;74:41-8 pubmed publisher
    ..We found that two out of eight HMG samples showed trisomy of chromosome 1q, which encompasses many genes, including AKT3, a gene known to regulate brain size. A third case showed a known activating mutation in AKT3 (c.49G?A, creating p...
  7. Gangwani M, Noel R, Shah A, Rivera Amill V, Kumar A. Human immunodeficiency virus type 1 viral protein R (Vpr) induces CCL5 expression in astrocytes via PI3K and MAPK signaling pathways. J Neuroinflammation. 2013;10:136 pubmed publisher
    ..Furthermore, this effect was observed to be mediated by transcription factors NF-?B and AP-1 and involved the p38-MAPK and PI3K/Akt pathway. ..
  8. Mure H, Matsuzaki K, Kitazato K, Mizobuchi Y, Kuwayama K, Kageji T, et al. Akt2 and Akt3 play a pivotal role in malignant gliomas. Neuro Oncol. 2010;12:221-32 pubmed publisher
    ..However, the expression profiles of the Akt isoforms Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma and their functional roles in malignant glioma are not well understood...
  9. Liu X, Shah A, Gangwani M, Silverstein P, Fu M, Kumar A. HIV-1 Nef induces CCL5 production in astrocytes through p38-MAPK and PI3K/Akt pathway and utilizes NF-kB, CEBP and AP-1 transcription factors. Sci Rep. 2014;4:4450 pubmed publisher
    ..The results demonstrated that the PI3K/Akt and p38 MAPK pathways, along with the transcription factors NF-?B, CEBP, and AP-1, are involved in Nef-induced CCL5 production in astrocytes. ..

More Information

Publications107 found, 100 shown here

  1. Borgatti P, Zauli G, Colamussi M, Gibellini D, Previati M, Cantley L, et al. Extracellular HIV-1 Tat protein activates phosphatidylinositol 3- and Akt/PKB kinases in CD4+ T lymphoblastoid Jurkat cells. Eur J Immunol. 1997;27:2805-11 pubmed
    ..Taken together, these data suggest that the anti-apoptotic activity of low concentrations of Tat protein on Jurkat cells is mediated by a PI 3-kinase/Akt pathway. ..
  2. Nakatani K, Thompson D, Barthel A, Sakaue H, Liu W, Weigel R, et al. Up-regulation of Akt3 in estrogen receptor-deficient breast cancers and androgen-independent prostate cancer lines. J Biol Chem. 1999;274:21528-32 pubmed
    We measured the insulin-stimulated amount of Akt1, Akt2, and Akt3 enzymatic activities in four breast cancer cell lines and three prostate cancer cell lines...
  3. Zinda M, Johnson M, Paul J, Horn C, Konicek B, Lu Z, et al. AKT-1, -2, and -3 are expressed in both normal and tumor tissues of the lung, breast, prostate, and colon. Clin Cancer Res. 2001;7:2475-9 pubmed
    ..Our data show that both normal and tumor tissues express all three of the AKT isoforms and indicate that tumorigenesis does not involve a dramatic shift in the RNA expression patterns of the three AKT isoforms. ..
  4. Chugh P, Fan S, Planelles V, Maggirwar S, Dewhurst S, Kim B. Infection of human immunodeficiency virus and intracellular viral Tat protein exert a pro-survival effect in a human microglial cell line. J Mol Biol. 2007;366:67-81 pubmed
    ..We propose that the expression of Tat may enable HIV-1 infected microglia to survive throughout the course of infection, leading to persistent HIV-1 production and infection in the central nervous system. ..
  5. Deregibus M, Cantaluppi V, Doublier S, Brizzi M, Deambrosis I, Albini A, et al. HIV-1-Tat protein activates phosphatidylinositol 3-kinase/ AKT-dependent survival pathways in Kaposi's sarcoma cells. J Biol Chem. 2002;277:25195-202 pubmed
  6. Stahl J, Sharma A, Cheung M, Zimmerman M, Cheng J, Bosenberg M, et al. Deregulated Akt3 activity promotes development of malignant melanoma. Cancer Res. 2004;64:7002-10 pubmed
    ..We report that selective activation of the Akt3 protein promotes cell survival and tumor development in 43 to 60% of nonfamilial melanomas...
  7. Shin S, Asano T, Yao Y, Zhang R, Claret F, Korc M, et al. Activator protein-1 has an essential role in pancreatic cancer cells and is regulated by a novel Akt-mediated mechanism. Mol Cancer Res. 2009;7:745-754 pubmed publisher
    ..Collectively, our findings indicate that AP-1 has an important function in pancreatic cancer cells and provide evidence for a previously unknown Akt-mediated mechanism of c-Jun activation. ..
  8. Santi S, Lee H. The Akt isoforms are present at distinct subcellular locations. Am J Physiol Cell Physiol. 2010;298:C580-91 pubmed publisher
    ..Akt2 was colocalized with the mitochondria, while Akt3 was localized in both the nucleus and nuclear membrane...
  9. Zhou F, Xue M, Qin D, Zhu X, Wang C, Zhu J, et al. HIV-1 Tat promotes Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6-induced angiogenesis and tumorigenesis by regulating PI3K/PTEN/AKT/GSK-3? signaling pathway. PLoS ONE. 2013;8:e53145 pubmed publisher
    ..Together, these results provide the first evidence that Tat might contribute to KS pathogenesis by synergizing with vIL-6, and identify PI3K/AKT pathway as a potential therapeutic target in AIDS-related KS patients. ..
  10. Brodbeck D, Cron P, Hemmings B. A human protein kinase Bgamma with regulatory phosphorylation sites in the activation loop and in the C-terminal hydrophobic domain. J Biol Chem. 1999;274:9133-6 pubmed
    ..This contrasts with rat PKBgamma, which is thought to be regulated by 3-phosphoinositide-dependent protein kinase 1 alone. ..
  11. Nawa M, Kanekura K, Hashimoto Y, Aiso S, Matsuoka M. A novel Akt/PKB-interacting protein promotes cell adhesion and inhibits familial amyotrophic lateral sclerosis-linked mutant SOD1-induced neuronal death via inhibition of PP2A-mediated dephosphorylation of Akt/PKB. Cell Signal. 2008;20:493-505 pubmed
    ..We recently demonstrated that activation of Akt3 by the autosomal-recessive familial amyotrophic lateral sclerosis (ALS)-linked gene 2 (ALS2) product, alsinLF, led ..
  12. Tachado S, Li X, Swan K, Patel N, Koziel H. Constitutive activation of phosphatidylinositol 3-kinase signaling pathway down-regulates TLR4-mediated tumor necrosis factor-alpha release in alveolar macrophages from asymptomatic HIV-positive persons in vitro. J Biol Chem. 2008;283:33191-8 pubmed publisher
  13. Fornari F, Milazzo M, Chieco P, Negrini M, Marasco E, Capranico G, et al. In hepatocellular carcinoma miR-519d is up-regulated by p53 and DNA hypomethylation and targets CDKN1A/p21, PTEN, AKT3 and TIMP2. J Pathol. 2012;227:275-85 pubmed publisher
    ..These functions are, at least in part, exerted through the direct targeting of CDKN1A/p21, PTEN, AKT3 and TIMP2...
  14. Nookala A, Shah A, Noel R, Kumar A. HIV-1 Tat-mediated induction of CCL5 in astrocytes involves NF-?B, AP-1, C/EBP? and C/EBP? transcription factors and JAK, PI3K/Akt and p38 MAPK signaling pathways. PLoS ONE. 2013;8:e78855 pubmed publisher
    ..This was further confirmed at transcriptional level that AP-1, C/EBP? and C/EBP? were involved in CCL5 up-regulation. ..
  15. Zhu X, Guo Y, Yao S, Yan Q, Xue M, Hao T, et al. Synergy between Kaposi's sarcoma-associated herpesvirus (KSHV) vIL-6 and HIV-1 Nef protein in promotion of angiogenesis and oncogenesis: role of the AKT signaling pathway. Oncogene. 2014;33:1986-96 pubmed publisher
    ..These novel findings also suggest that targeting the PI3K/AKT signal may be a potentially effective therapeutic approach in AIDS-KS patients. ..
  16. Maniam J, Antoniadis C, Le V, Morris M. A diet high in fat and sugar reverses anxiety-like behaviour induced by limited nesting in male rats: Impacts on hippocampal markers. Psychoneuroendocrinology. 2016;68:202-9 pubmed publisher
    ..Interestingly, HFHS diet and LN exposure independently reduced expression of Akt3 mRNA, a key gene involved post-natal brain development...
  17. Jiao B, Zhang X, Wang S, Wang L, Luo Z, Zhao H, et al. MicroRNA-221 regulates proliferation of bovine mammary gland epithelial cells by targeting the STAT5a and IRS1 genes. J Dairy Sci. 2019;102:426-435 pubmed publisher
    ..Furthermore, expression levels of the downstream genes SOCS3, AKT3, and mTOR that are regulated by STAT5a and IRS1 in the JAK-STAT and PI3K-Akt/mTOR signaling pathways, were also ..
  18. Farris T, Dunphy P, Zhu B, Kibler C, McBride J. Ehrlichia chaffeensis TRP32 is a Nucleomodulin that Directly Regulates Expression of Host Genes Governing Differentiation and Proliferation. Infect Immun. 2016;84:3182-3194 pubmed publisher
    ..on all chromosomes and included several global regulators of proliferation and inflammation such as FOS and JUN, AKT3 and NRAS, and non-coding RNA genes, miRNA 21 and miRNA 142...
  19. Jiang W, Guo Y, Yang K, Shi Q, Yang J. Insights into Body Size Evolution: A Comparative Transcriptome Study on Three Species of Asian Sisoridae Catfish. Int J Mol Sci. 2019;20: pubmed publisher
    ..total, 20 size-related candidate genes (including two growth modulators: the serine/threonine-protein kinases 3 (AKT3) and adaptor protein 1 (SH2B1), and a crucial pyruvate kinase (PKM2A)) were identified by ..
  20. Roudi R, Madjd Z, Ebrahimi M, Najafi A, Korourian A, Shariftabrizi A, et al. Evidence for embryonic stem-like signature and epithelial-mesenchymal transition features in the spheroid cells derived from lung adenocarcinoma. Tumour Biol. 2016;37:11843-11859 pubmed
    ..PI3/AKT3, as the most common up-regulated pathway, and other pathways related to aggressive tumor behavior and EMT process ..
  21. Wang K, Zhang Z, Liu K, Yang X, Zou H, Zhou J, et al. Neat1-miRNA204-5p-PI3K-AKT axis as a potential mechanism for Photodynamic Therapy treated Colitis in Mice. Photodiagnosis Photodyn Ther. 2018;: pubmed publisher
    ..Additionally, the decreased expression level of the AKT3, p-AKT3, PI3K, p-PI3K protein were confirmed...
  22. Chang C, Yang J, Zhao W, Li Y, Guo P, Li M, et al. Gene expression profiling analysis of 5-hydroxytryptamine signaling pathway in rat regenerating liver and different types of liver cells. Genet Mol Res. 2015;14:3409-20 pubmed publisher
    ..endothelial cells through the STAT3 signaling pathway, and proliferation and apoptosis of pit cells through the AKT3 signaling pathway...
  23. Pectasides D, Kotoula V, Papaxoinis G, Alexopoulou Z, Dervenis C, Samantas E, et al. Expression Patterns of Growth and Survival Genes with Prognostic Implications in Advanced Pancreatic Cancer. Anticancer Res. 2016;36:6347-6356 pubmed
    ..thymoma viral oncogene homolog 1 (AKT1), AKT serine/threonine kinase 2 (AKT2), AKT serine/threonine kinase 3 (AKT3), cyclin D1 (CCND1), epidermal growth factor receptor (EGFR), mitogen-activated protein kinase 1 (MAPK1), ..
  24. Xie X, Man X, Zhu Z, Yuan D, Huang S. Tumor suppressor RIZ1 in obesity and the PI3K/AKT/mTOR pathway. Obesity (Silver Spring). 2016;24:389-97 pubmed publisher
    ..The PI3K/AKT/mTOR pathway was activated in the Riz1(-/-) mice fed a HF diet with higher Akt3 mRNA levels and increased phosphorylation of AKT (Ser473), mTOR, and S6...
  25. Kamalden T, Macgregor Das A, Kannan S, Dunkerly Eyring B, Khaliddin N, Xu Z, et al. Exosomal MicroRNA-15a Transfer from the Pancreas Augments Diabetic Complications by Inducing Oxidative Stress. Antioxid Redox Signal. 2017;27:913-930 pubmed publisher
    ..to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death...
  26. Weihbrecht K, Goar W, Carter C, Sheffield V, Seo S. Genotypic and phenotypic characterization of the Sdccag8Tn(sb-Tyr)2161B.CA1C2Ove mouse model. PLoS ONE. 2018;13:e0192755 pubmed publisher
    ..we found that SBT insertion resulted in a deletion of multiple exons from both Sdccag8 and its neighboring gene Akt3. We ascribe the patterning defects in the limb and the secondary palate as well as lung abnormalities to loss of ..
  27. Vergadi E, Ieronymaki E, Lyroni K, Vaporidi K, Tsatsanis C. Akt Signaling Pathway in Macrophage Activation and M1/M2 Polarization. J Immunol. 2017;198:1006-1014 pubmed publisher
    ..Akt is a family of three serine-threonine kinases, Akt1, Akt2, and Akt3. Generation of mice lacking individual Akt, PI3K, or mTOR isoforms and utilization of RNA interference technology ..
  28. Bowers L, Rossi E, McDonell S, Doerstling S, Khatib S, Lineberger C, et al. Leptin Signaling Mediates Obesity-Associated CSC Enrichment and EMT in Preclinical TNBC Models. Mol Cancer Res. 2018;16:869-879 pubmed publisher
    ..cell viability, migration, invasion, and CSC- and EMT-related gene expression, including Foxc2, Twist2, Vim, Akt3, and Sox2 In E-Wnt cells, knockdown of leptin receptor ablated these procancer effects induced by DIO ..
  29. Takagi M, Dobashi K, Nagahara K, Kato M, Nishimura G, Fukuzawa R, et al. A novel de novo germline mutation Glu40Lys in AKT3 causes megalencephaly with growth hormone deficiency. Am J Med Genet A. 2017;173:1071-1076 pubmed publisher
    Germline or somatic gain-of-function mutations in the v-akt murine thymoma viral oncogene homolog 3 (AKT3) have been reported to cause syndromic megalencephaly. We describe a novel germline mutation, p.Glu40Lys, in AKT3...
  30. Sozopoulos E, Litsiou H, Voutsinas G, Mitsiades N, Anagnostakis N, Tseva T, et al. Mutational and immunohistochemical study of the PI3K/Akt pathway in papillary thyroid carcinoma in Greece. Endocr Pathol. 2010;21:90-100 pubmed publisher
    ..We evaluated the presence of mutations in PIK3CA (exons 9 and 20), AKT1 (exons 6-11), AKT2 (exons 6-11), AKT3 (exons 5-10), PTEN (exons 3-8), and PDPK1 (exons 4-10) genes in 83 papillary thyroid carcinomas by DNA sequencing...
  31. Shah A, Silverstein P, Kumar S, Singh D, Kumar A. Synergistic cooperation between methamphetamine and HIV-1 gsp120 through the P13K/Akt pathway induces IL-6 but not IL-8 expression in astrocytes. PLoS ONE. 2012;7:e52060 pubmed publisher
    ..This study therefore provides novel information regarding the interaction between MA and gp120 in terms of the expression of IL-6 and the mechanisms underlying potential synergy between MA and gp120 in astrocytes...
  32. Wang L, Huang D, Jiang Z, Luo Y, Norris C, Zhang M, et al. Akt3 is responsible for the survival and proliferation of embryonic stem cells. Biol Open. 2017;6:850-861 pubmed publisher
    ..However, the distinct roles of Akt isoforms (Akt1, Akt2, and Akt3) in pluripotent stem cell maintenance are not fully defined...
  33. Bomben R, Ferrero S, D Agaro T, Dal Bo M, Re A, Evangelista A, et al. A B-cell receptor-related gene signature predicts survival in mantle cell lymphoma: results from the Fondazione Italiana Linfomi MCL-0208 trial. Haematologica. 2018;103:849-856 pubmed publisher
    ..The prediction model based on the quantitative real-time PCR values of six representative genes (AKT3, BCL2, BTK, CD79B, PIK3CD, and SYK), was used to classify the 83 cases (43 B-cell receptorlow ..
  34. Kaul M, Ma Q, Medders K, Desai M, Lipton S. HIV-1 coreceptors CCR5 and CXCR4 both mediate neuronal cell death but CCR5 paradoxically can also contribute to protection. Cell Death Differ. 2007;14:296-305 pubmed
    ..This finding suggests that CCR5 ligands can protect neurons at least, in part, by modulating CXCR4-mediated toxicity through heterologous desensitization. ..
  35. Zhang H, Sang W, Ruan Z, Wang Y. Akt/Nox2/NF-?B signaling pathway is involved in Tat-induced HIV-1 long terminal repeat (LTR) transactivation. Arch Biochem Biophys. 2011;505:266-72 pubmed publisher
  36. Wang L, Cheng S, Yin Z, Xu C, Lu S, Hou J, et al. Conditional inactivation of Akt three isoforms causes tau hyperphosphorylation in the brain. Mol Neurodegener. 2015;10:33 pubmed publisher
    ..In contrast, no significant changes on p-tau levels were found in Akt1(-/-), Akt2(-/-) or Akt3(-/-) mice. Akt may regulate tau phosphorylation in the adult brain by affecting activities for PKA and GSK3α.
  37. Stavrovskaya A, Shushanov S, Rybalkina E. Problems of Glioblastoma Multiforme Drug Resistance. Biochemistry (Mosc). 2016;81:91-100 pubmed publisher
    ..and proteins MGMT, IDH1/2, YB-1, MELK, MVP/LRP, MDR1 (ABCB1), and genes encoding other ABC transporters as well as Akt3 kinase in developing resistance of GBL to TMZ are discussed...
  38. Kang Y, Digicaylioglu M, Russo R, Kaul M, Achim C, Fletcher L, et al. Erythropoietin plus insulin-like growth factor-I protects against neuronal damage in a murine model of human immunodeficiency virus-associated neurocognitive disorders. Ann Neurol. 2010;68:342-52 pubmed publisher
    ..This combination peptide therapy should therefore be tested in humans with HAND. ..
  39. Malik S, Saha R, Seth P. Involvement of extracellular signal-regulated kinase (ERK1/2)-p53-p21 axis in mediating neural stem/progenitor cell cycle arrest in co-morbid HIV-drug abuse exposure. J Neuroimmune Pharmacol. 2014;9:340-53 pubmed publisher
  40. Zhao B, Shah P, Qiang L, He T, Budanov A, He Y. Distinct Role of Sesn2 in Response to UVB-Induced DNA Damage and UVA-Induced Oxidative Stress in Melanocytes. Photochem Photobiol. 2017;93:375-381 pubmed publisher
    ..UVB induces Sesn2 expression through the p53 and AKT3 pathways. Sesn2 negatively regulates UVB-induced DNA damage repair...
  41. Zhu L, Zhou J, Zhang J, Wang J, Wang Z, Pan M, et al. MiR-15b-5p Regulates Collateral Artery Formation by Targeting AKT3 (Protein Kinase B-3). Arterioscler Thromb Vasc Biol. 2017;37:957-968 pubmed publisher
    ..We identified AKT3 (protein kinase B-3) as a direct target of miR-15b-5p...
  42. Ding L, Zhang L, Kim M, Byzova T, Podrez E. Akt3 kinase suppresses pinocytosis of low-density lipoprotein by macrophages via a novel WNK/SGK1/Cdc42 protein pathway. J Biol Chem. 2017;292:9283-9293 pubmed publisher
    ..We have found previously that increased lipoprotein uptake via the receptor-independent process in Akt3 kinase-deficient macrophages contributes to increased atherosclerosis in Akt3-/- mice...
  43. Tokuda E, Fujita N, Oh hara T, Sato S, Kurata A, Katayama R, et al. Casein kinase 2-interacting protein-1, a novel Akt pleckstrin homology domain-interacting protein, down-regulates PI3K/Akt signaling and suppresses tumor growth in vivo. Cancer Res. 2007;67:9666-76 pubmed
    ..CKIP-1 formed a complex with each Akt isoform (Akt1, Akt2, and Akt3) via its NH2 terminus...
  44. Peviani M, Tortarolo M, Battaglia E, Piva R, Bendotti C. Specific induction of Akt3 in spinal cord motor neurons is neuroprotective in a mouse model of familial amyotrophic lateral sclerosis. Mol Neurobiol. 2014;49:136-48 pubmed publisher
    ..We demonstrate that specific expression of constitutively activated Akt3 in motor neurons through the use of the promoter of homeobox gene Hb9 prevents neuronal loss induced by SOD1...
  45. O Hurley G, Daly E, O Grady A, Cummins R, Quinn C, Flanagan L, et al. Investigation of molecular alterations of AKT-3 in triple-negative breast cancer. Histopathology. 2014;64:660-70 pubmed publisher
    ..AKT-3 amplification could represent a potentially relevant oncogenic event in a subset of TNBCs that may, in turn, select cells sensitive to Akt-3 inhibitors. ..
  46. Paul Samojedny M, Pudełko A, Kowalczyk M, Fila Daniłow A, Suchanek Raif R, Borkowska P, et al. Knockdown of AKT3 and PI3KCA by RNA interference changes the expression of the genes that are related to apoptosis and autophagy in T98G glioblastoma multiforme cells. Pharmacol Rep. 2015;67:1115-23 pubmed publisher
    ..The current study was undertaken to examine the effect of the siRNAs that target AKT3 and PI3KCA genes on the apoptosis and autophagy of T98G cells...
  47. Kumar S, Tomita Y, Wrin J, Bruhn M, Swalling A, Mohammed M, et al. High early growth response 1 (EGR1) expression correlates with resistance to anti-EGFR treatment in vitro and with poorer outcome in metastatic colorectal cancer patients treated with cetuximab. Clin Transl Oncol. 2017;19:718-726 pubmed publisher
    ..EGR1 (early growth response protein 1), HBEGF (heparin-binding epidermal growth factor-like growth factor), and AKT3 (AKT serine/threonine kinase 3)...
  48. Rivière J, Mirzaa G, O Roak B, Beddaoui M, Alcantara D, Conway R, et al. De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat Genet. 2012;44:934-40 pubmed publisher
    ..These include 2 mutations in AKT3, 1 recurrent mutation in PIK3R2 in 11 unrelated families with MPPH and 15 mostly postzygotic mutations in PIK3CA in ..
  49. Kouwenhoven A, Minassian V, Marsh J. HIV-1 Nef mediates Pak phosphorylation of Mek1 serine298 and elicits an active phospho-state of Pak2. Curr HIV Res. 2013;11:198-209 pubmed
    ..This phosphorylation is through a Pak and Rac activity. We also find that Pak2 in Nef expressing cells is phosphorylated on serine192/197, the first biochemical description of the Nef-mediated activation state for this kinase. ..
  50. Qin B, Liu J, Liu S, Li B, Ren J. MiR-20b targets AKT3 and modulates vascular endothelial growth factor-mediated changes in diabetic retinopathy. Acta Biochim Biophys Sin (Shanghai). 2016;48:732-40 pubmed publisher
    ..Luciferase reported assay showed that AKT3 is a target of miR-20b...
  51. Thompson S, Callstrom M, Jondal D, Butters K, Knudsen B, Anderson J, et al. Heat Stress-Induced PI3K/mTORC2-Dependent AKT Signaling Is a Central Mediator of Hepatocellular Carcinoma Survival to Thermal Ablation Induced Heat Stress. PLoS ONE. 2016;11:e0162634 pubmed publisher
    ..in primary human HCCs and that overexpression of AKT correlates with worse tumor biology and pathologic features (AKT3) and prognosis (AKT1)...
  52. Matheny R, Carrigan C, Abdalla M, Geddis A, Leandry L, Aguilar C, et al. RNA transcript expression of IGF-I/PI3K pathway components in regenerating skeletal muscle is sensitive to initial injury intensity. Growth Horm IGF Res. 2017;32:14-21 pubmed publisher
    ..significantly increased expression of Igf1, Igf2, Igf1r, Igf2r, Pik3cb, Pik3cd, Pik3cg, Pik3r1, Pik3r5, Akt1, and Akt3 in response to either 5s or 10s injury compared to uninjured control muscle...
  53. Horman S, Janas M, Litterst C, Wang B, Macrae I, Sever M, et al. Akt-mediated phosphorylation of argonaute 2 downregulates cleavage and upregulates translational repression of MicroRNA targets. Mol Cell. 2013;50:356-67 pubmed publisher
    ..Here we report that the proto-oncogene Akt-3/PKB? (Akt3) phosphorylates Argonaute 2 (Ago2) at S387, which downregulates cleavage and upregulates translational repression ..
  54. Grabinski N, Möllmann K, Milde Langosch K, Muller V, Schumacher U, Brandt B, et al. AKT3 regulates ErbB2, ErbB3 and estrogen receptor ? expression and contributes to endocrine therapy resistance of ErbB2(+) breast tumor cells from Balb-neuT mice. Cell Signal. 2014;26:1021-9 pubmed publisher
    ..AKT isoform specific in vitro kinase assays revealed that AKT3 is activated in Balb-neuT breast tumors in comparison to normal murine breast tissue...
  55. Grottke A, Ewald F, Lange T, Nörz D, Herzberger C, Bach J, et al. Downregulation of AKT3 Increases Migration and Metastasis in Triple Negative Breast Cancer Cells by Upregulating S100A4. PLoS ONE. 2016;11:e0146370 pubmed publisher
    ..However, there is emerging data that single AKT isoforms (i.e. AKT1, AKT2 and AKT3) have different or even opposing functions in the regulation of cancer cell migration in vitro, giving rise to the ..
  56. Miao L, Yang L, Huang H, Liang F, Ling C, Hu Y. mTORC1 is necessary but mTORC2 and GSK3? are inhibitory for AKT3-induced axon regeneration in the central nervous system. elife. 2016;5:e14908 pubmed publisher
    ..We found that the predominant AKT isoform in CNS, AKT3, induces much more robust axon regeneration than AKT1 and that activation of mTORC1 and inhibition of GSK3? are two ..
  57. Lim J, Gopalappa R, Kim S, Ramakrishna S, Lee M, Kim W, et al. Somatic Mutations in TSC1 and TSC2 Cause Focal Cortical Dysplasia. Am J Hum Genet. 2017;100:454-472 pubmed publisher
    ..capture and amplicon sequencing (read depth of 100×-20,012×) of five important mTOR pathway genes-PIK3CA, PIK3R2, AKT3, TSC1, and TSC2-by using paired brain and saliva samples from 40 FCDII individuals negative for MTOR mutations...
  58. Li W, Zhang J, Bottaro D, Pierce J. Identification of serine 643 of protein kinase C-delta as an important autophosphorylation site for its enzymatic activity. J Biol Chem. 1997;272:24550-5 pubmed
    ..Taken together, our results demonstrate that serine 643 of PKC-delta is a major autophosphorylation site, and phosphorylation of this site plays an important role in controlling its enzymatic activity and biological function. ..
  59. Pham N, Tsao M, Cao P, Hedley D. Dissociation of gemcitabine sensitivity and protein kinase B signaling in pancreatic ductal adenocarcinoma models. Pancreas. 2007;35:e16-26 pubmed
    ..These results suggested that gemcitabine efficacy involving the PKB pathway depends on PKB activity, its mechanisms of enhanced activity, as well as its function in a signaling network. ..
  60. Umemura S, Mimaki S, Makinoshima H, Tada S, Ishii G, Ohmatsu H, et al. Therapeutic priority of the PI3K/AKT/mTOR pathway in small cell lung cancers as revealed by a comprehensive genomic analysis. J Thorac Oncol. 2014;9:1324-31 pubmed publisher
    ..alterations in the PI3K/AKT/mTOR pathway were detected in 36% of the tumors: PIK3CA, 6%; PTEN, 4%; AKT2, 9%; AKT3, 4%; RICTOR, 9%; and mTOR, 4%. Furthermore, the individual changes in this pathway were mutually exclusive...
  61. Guo J, Chakraborty A, Liu P, Gan W, Zheng X, Inuzuka H, et al. pVHL suppresses kinase activity of Akt in a proline-hydroxylation-dependent manner. Science. 2016;353:929-32 pubmed publisher
    ..Our results show that microenvironmental changes, such as hypoxia, can affect tumor behaviors by altering Akt activation, which has a critical role in tumor growth and therapeutic resistance. ..
  62. Nakatani K, Sakaue H, Thompson D, Weigel R, Roth R. Identification of a human Akt3 (protein kinase B gamma) which contains the regulatory serine phosphorylation site. Biochem Biophys Res Commun. 1999;257:906-10 pubmed
    ..However, the reported sequence of the rat Akt3 protein differed significantly from this in that it lacked 25 amino acids in the C-terminal region, including this ..
  63. Sandirasegarane L, Kester M. Enhanced stimulation of Akt-3/protein kinase B-gamma in human aortic smooth muscle cells. Biochem Biophys Res Commun. 2001;283:158-63 pubmed
    ..Moreover, these data suggest that PI-3K-dependent activation of Akt-3 may play a major role in VSMC proliferation. ..
  64. Laine J, Künstle G, Obata T, Noguchi M. Differential regulation of Akt kinase isoforms by the members of the TCL1 oncogene family. J Biol Chem. 2002;277:3743-51 pubmed
    ..Here we show that, in contrast to Akt1 and Akt2, which bind to all members of the TCL1 family, Akt3 specifically interacts with TCL1 but not with MTCP1 or TCL1b...
  65. Peng L, Chen G, Zhu Z, Shen Z, Du C, Zang R, et al. Circular RNA ZNF609 functions as a competitive endogenous RNA to regulate AKT3 expression by sponging miR-150-5p in Hirschsprung's disease. Oncotarget. 2017;8:808-818 pubmed publisher
    ..We screened out several putative cir-ZNF609 ceRNAs of which the AKT3 transcript was selected...
  66. Zhang Y, Guo X, Yang M, Yu L, Li Z, Lin N. Identification of AKT kinases as unfavorable prognostic factors for hepatocellular carcinoma by a combination of expression profile, interaction network analysis and clinical validation. Mol Biosyst. 2014;10:215-22 pubmed publisher
    ..Among 331 candidate HCC markers, the three AKT kinase family members (AKT1-AKT3) were selected for clinical validation by immunohistochemistry analysis using 130 HCC specimens and matched ..
  67. Baek S, Copeland B, Yun E, Kwon S, Guemez Gamboa A, Schaffer A, et al. An AKT3-FOXG1-reelin network underlies defective migration in human focal malformations of cortical development. Nat Med. 2015;21:1445-54 pubmed publisher
    ..FMCD-affected brain, we found that cells showing activation of the PI3K-AKT-mTOR pathway were enriched for the AKT3(E17K) mutation...
  68. Vergara D, Simeone P, Toraldo D, Del Boccio P, Vergaro V, Leporatti S, et al. Resveratrol downregulates Akt/GSK and ERK signalling pathways in OVCAR-3 ovarian cancer cells. Mol Biosyst. 2012;8:1078-87 pubmed publisher
    ..Thus, resveratrol shows antitumor activity in human ovarian cancer cell lines targeting signalling pathway involved in cell proliferation and drug-resistance. ..
  69. Wu H, Xiao Z, Zhang H, Wang K, Liu W, Hao Q. MiR-489 modulates cisplatin resistance in human ovarian cancer cells by targeting Akt3. Anticancer Drugs. 2014;25:799-809 pubmed publisher
    ..b>Akt3 is validated as a direct target of miR-489 in SKOV3, OVCAR3, SKOV3/CDDP and OVCAR3/CDDP cells...
  70. Clark A, Toker A. Signalling specificity in the Akt pathway in breast cancer. Biochem Soc Trans. 2014;42:1349-55 pubmed publisher
    ..Three isoforms of the serine/threonine protein kinase Akt (Akt1, Akt2 and Akt3) function to regulate cell survival, growth, proliferation and metabolism...
  71. Valls Serón M, Ferwerda B, Engelen Lee J, Geldhoff M, Jaspers V, Zwinderman A, et al. V-akt murine thymoma viral oncogene homolog 3 (AKT3) contributes to poor disease outcome in humans and mice with pneumococcal meningitis. Acta Neuropathol Commun. 2016;4:50 pubmed publisher
    ..dynactin 4 (DCTN4), retinoic acid early transcript 1E (RAET1E), and V-akt murine thymoma viral oncogene homolog 3 (AKT3) to be associated with unfavourable outcome in patients with pneumococcal meningitis...
  72. Nonomiya Y, Noguchi K, Tanaka N, Kasagaki T, Katayama K, Sugimoto Y. Effect of AKT3 expression on MYC- and caspase-8-dependent apoptosis caused by polo-like kinase inhibitors in HCT 116 cells. Cancer Sci. 2016;107:1877-1887 pubmed publisher
    ..We also showed that the expression of P-glycoprotein (P-GP) and AKT3 was upregulated, whereas that of MYC was downregulated in some BI 2536-resistant cell lines...
  73. Guo T, Sakai A, Afsari B, Considine M, Danilova L, Favorov A, et al. A Novel Functional Splice Variant of AKT3 Defined by Analysis of Alternative Splice Expression in HPV-Positive Oropharyngeal Cancers. Cancer Res. 2017;77:5248-5258 pubmed publisher
    ..correlation between promoter methylation and expression of an alternative transcriptional start site, including AKT3 The novel AKT3 transcriptional variant and methylation changes were confirmed using qRT-PCR and qMSP ..
  74. Hodgkinson C, Sale E, Sale G. Characterization of PDK2 activity against protein kinase B gamma. Biochemistry. 2002;41:10351-9 pubmed
  75. Tiwari G, Sakaue H, Pollack J, Roth R. Gene expression profiling in prostate cancer cells with Akt activation reveals Fra-1 as an Akt-inducible gene. Mol Cancer Res. 2003;1:475-84 pubmed
    ..This construct was found to be directly induced 4- to 5-fold by co-transfection with constitutively active Akt3 but not kinase dead Akt...
  76. Endersby R, Zhu X, Hay N, Ellison D, Baker S. Nonredundant functions for Akt isoforms in astrocyte growth and gliomagenesis in an orthotopic transplantation model. Cancer Res. 2011;71:4106-16 pubmed publisher
    ..In addition, Akt3 was required for anchorage-independent growth of transformed astrocytes and human glioma cells, and Akt3 loss ..
  77. Jansen L, Mirzaa G, Ishak G, O Roak B, Hiatt J, Roden W, et al. PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia. Brain. 2015;138:1613-28 pubmed publisher
    ..We identified mosaic activating mutations in PIK3CA and AKT3 in this cohort, including cancer-associated hotspot PIK3CA mutations in dysplastic megalencephaly, ..
  78. Long M, Parvez S, Zhao Y, Surya S, Wang Y, Zhang S, et al. Akt3 is a privileged first responder in isozyme-specific electrophile response. Nat Chem Biol. 2017;13:333-338 pubmed publisher
    ..Methods to study this phenomenon are underdeveloped. Here we use a redox-targeting screen to reveal that Akt3 is a first-responding isozyme sensing native electrophilic lipids...
  79. Zhang X, Zhang S, Yamane H, Wahl R, Ali A, Lofgren J, et al. Kinetic mechanism of AKT/PKB enzyme family. J Biol Chem. 2006;281:13949-56 pubmed
    ..AKT2 showed the highest Km value for ATP, and AKT3 showed the highest kcat value...
  80. Nawa M, Matsuoka M. KCTD20, a relative of BTBD10, is a positive regulator of Akt. BMC Biochem. 2013;14:27 pubmed publisher
    ..KCTD20 was ubiquitously expressed in non-nervous as well as nervous tissues. KCTD20 is a positive regulator of Akt and may play an important role in regulating the death and growth of some non-nervous and nervous cells. ..
  81. Paul Samojedny M, Pudełko A, Kowalczyk M, Fila Daniłow A, Suchanek Raif R, Borkowska P, et al. Combination Therapy with AKT3 and PI3KCA siRNA Enhances the Antitumor Effect of Temozolomide and Carmustine in T98G Glioblastoma Multiforme Cells. BioDrugs. 2016;30:129-44 pubmed publisher
    ..The current study was undertaken to examine the effect of small interfering RNA (siRNA) targeting the AKT3 and PIK3CA genes on the susceptibility of T98G cells to temozolomide (TMZ) and carmustine (BCNU)...
  82. Bhardwaj A, Singh H, Rajapakshe K, Tachibana K, Ganesan N, Pan Y, et al. Regulation of miRNA-29c and its downstream pathways in preneoplastic progression of triple-negative breast cancer. Oncotarget. 2017;8:19645-19660 pubmed publisher
    ..2 (TGIF2), CAMP-responsive element binding protein 5 (CREB5), and V-Akt murine thymoma viral oncogene homolog 3 (AKT3)...
  83. Kapasi A, Fan S, Singhal P. Role of 14-3-3epsilon, c-Myc/Max, and Akt phosphorylation in HIV-1 gp 120-induced mesangial cell proliferation. Am J Physiol Renal Physiol. 2001;280:F333-42 pubmed
    ..These results suggest that HIV-1 gp 120 induces alterations in conflicting survival signaling pathways that contribute to the potential dual effects of gp 120 in promoting or inhibiting HMC proliferation...
  84. Boufraqech M, Zhang L, Jain M, Patel D, Ellis R, Xiong Y, et al. miR-145 suppresses thyroid cancer growth and metastasis and targets AKT3. Endocr Relat Cancer. 2014;21:517-31 pubmed publisher
    ..miR-145 overexpression also inhibited the PI3K/Akt pathway and directly targeted AKT3. In vivo, miR-145 overexpression decreased tumor growth and metastasis in a xenograft mouse model, and VEGF ..
  85. Zheng Y, Xu Z. MicroRNA-22 induces endothelial progenitor cell senescence by targeting AKT3. Cell Physiol Biochem. 2014;34:1547-55 pubmed publisher
    ..b>AKT3 was identified as a direct target of miR-22, and restoration of AKT3 expression attenuated the effects of miR-22 in ..
  86. Roy N, Bordoloi D, Monisha J, Padmavathi G, Kotoky J, Golla R, et al. Specific Targeting of Akt Kinase Isoforms: Taking the Precise Path for Prevention and Treatment of Cancer. Curr Drug Targets. 2017;18:421-435 pubmed publisher
    ..This review discusses the divergent roles of Akt isoforms comprehensively in different cancers and finding their immense prospects as potential targets for cancer prevention and treatment. ..
  87. Suyama K, Yao J, Liang H, Benard O, Loudig O, Amgalan D, et al. An Akt3 Splice Variant Lacking the Serine 472 Phosphorylation Site Promotes Apoptosis and Suppresses Mammary Tumorigenesis. Cancer Res. 2018;78:103-114 pubmed publisher
    The Akt pathway is a well-known promoter of tumor malignancy. Akt3 is expressed as two alternatively spliced variants, one of which lacks the key regulatory serine 472 phosphorylation site...
  88. Ye R, Wei B, Li S, Liu W, Liu J, Qiu L, et al. Expression of miR-195 is associated with chemotherapy sensitivity of cisplatin and clinical prognosis in gastric cancer. Oncotarget. 2017;8:97260-97272 pubmed publisher
    ..Subsequently, AKT3 was identified as the direct target gene of miR-195 by target gene prediction software, dual luciferase reporter ..
  89. Guda B, Pushkarev V, Zhuravel O, Kovalenko A, Pushkarev V, Taraschenko Y, et al. Protein kinase Akt activity in human thyroid tumors. Ukr Biochem J. 2016;88:90-5 pubmed publisher
    ..Apoptosis level detected in these tissues was not associated with the protein kinase activity either. Possible mechanisms of signaling cascade PI3K/Akt inhibition in thyroid tumors are discussed. ..
  90. Kanekura K, Hashimoto Y, Kita Y, Sasabe J, Aiso S, Nishimoto I, et al. A Rac1/phosphatidylinositol 3-kinase/Akt3 anti-apoptotic pathway, triggered by AlsinLF, the product of the ALS2 gene, antagonizes Cu/Zn-superoxide dismutase (SOD1) mutant-induced motoneuronal cell death. J Biol Chem. 2005;280:4532-43 pubmed
    ..Among three Akt family proteins, Akt3 is the major downstream mediator for alsinLF/Rac1-mediated neuroprotection, which is specifically effective against ..
  91. Kino T, De Martino M, Charmandari E, Ichijo T, Outas T, Chrousos G. HIV-1 accessory protein Vpr inhibits the effect of insulin on the Foxo subfamily of forkhead transcription factors by interfering with their binding to 14-3-3 proteins: potential clinical implications regarding the insulin resistance of HIV-1-infecte. Diabetes. 2005;54:23-31 pubmed
    ..Vpr thus may contribute to the tissue-selective insulin resistance often observed in HIV-1-infected individuals. ..
  92. Vanli G, Peltzer N, Dubuis G, Widmann C. The activity of the anti-apoptotic fragment generated by the caspase-3/p120 RasGAP stress-sensing module displays strict Akt isoform specificity. Cell Signal. 2014;26:2992-7 pubmed publisher
    ..These cellular processes are regulated by three distinct Akt isoforms: Akt1, Akt2 and Akt3. However, which of these isoforms are required for fragment N mediated protection have not been defined...