Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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AKT serine/threonine kinase 3(AKT3) AKT serine/threonine kinase 3(AKT3) Related Genes Homo sapiens
CYTOBAND 1q43-q44,
GENERIF_SUMMARY results show that a defect in the ability of insulin to activate Akt-2 and -3 may explain the impaired insulin-stimulated glucose transport in insulin resistance, The regulation by Akt3 was found to be due to two specific regions in the Fra-1 regulatory sequence which match Sp1 consensus sites, The above results indicate that PKB-Ser-473 and FAK-Tyr phosphorylation stimulated by TGF-beta1 are both dependent on cell adhesion., Targeted reduction of Akt3 activity with siRNA or by expressing active PTEN protein stimulated apoptotic signaling, which reduced cell survival by increasing apoptosis rates thereby inhibiting melanoma tumor development., Dysregulation of the PI 3-K/AKT/PTEN pathway may contribute to early head neck squamous cell carcinoma tumorigenesis., Rac1, PI3 kinase, and Akt3 have roles in an anti-apoptotic pathway triggered by ALS2 that antagonizes SOD1 mutant-induced motoneuronal cell death, activation of Akt signaling results in progression from adaptive to maladaptive cardiac hypertrophy, in breast cancer patients, Akt activation is associated with tumour proliferation and poor prognosis, particularly in the subset of patients with ErbB2-overexpressing tumours, AKT3 is highly expressed in 19 of 92 primary ovarian tumors, consistent with AKT3 playing a key role in the genesis of at least one subset of ovarian cancers., AKT3 represents an excellent candidate for developmental human MIC and ACC, and we suggest that haploinsufficiency causes both postnatal MIC and ACC., PKB[alpha] and/or PKB[gamma] and not PKB[beta] alone are involved in gemcitabine resistance mechanisms., Akt3 and mutant V600E B-Raf cooperate to promote early melanoma development., the first report of AKT mutations in melanoma, and the initial identification of an AKT3 mutation in any human cancer lineage, Bcr-Abl represses the expression of PHLPP1 and PHLPP2 and continuously activates Akt1, -2, and -3 via phosphorylation on Ser-473, resulting in the proliferation of CML cells, 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., Akt3 was located in the nucleus and nuclear membrane of human cell lines., In breast cancer AKT3 amplifications and AKT1 and AKT2 deletions were seen by FISH, Our data suggest that Akt2 and Akt3 play an important role in the viability of human malignant glioma cells, We evaluated the presence of mutations in PIK3CA, AKT1, AKT2, AKT3, PTEN, and PDPK1 genes in 83 papillary thyroid carcinomas, Studies indicate that three different isoforms Akt1, Akt2, and Akt3 have distinct expression patterns and functions., Mutant B-RAF melanoma cells ectopically expressing a constitutively activated form of Akt3 or endogenously expressing mutant Akt3 were protected from apoptosis induced by B-RAF knockdown or PLX4720 treatment., No AKT3 E17K mutation was detected in the 73 squamous cell carcinomas of the lung, Expression of matrix metalloproteinase-13 is controlled by IL-13 via PI3K/Akt3 and PKC-delta in normal human dermal fibroblasts., These findings suggest an important role for Akt3 in the regulation of RCAS1 and VEGF secretion in ovarian cancer cells., We did not find any mutation in the GNAQ, AKT3, and PIK3R1 genes in various types of thyroid cancer., Akt3 was required for anchorage-independent growth of transformed astrocytes and human glioma cells, Transcriptional activation of the Akt3 pathway indicates that it is involved in lumbar disc degeneration., Our data demonstrate that Akt1 and notably Akt3 regulate proliferation, survival, migration and EGF-mediated signal transduction in NSCLC-derived DTC, Akt3 plays an important and distinct role in platelet activation and in thrombosis., The prognostic impact of Akt (Akt1) phosphorylated at threonine308 and serine473, Akt2, Akt3, PI3K and PTEN, alone and in coexpression with ER and PgR in non-gastrointestinal stromal tumor soft tissue sarcomas., Resveratrol down-regulates the protein cyclin D1 and, in a concentration dependent manner, the phosphorylation levels of protein kinase B and glycogen synthase kinase-3beta in OVCAR-3 ovarian cancer cells., In hepatocellular carcinoma miR-519d is up-regulated by p53 and DNA hypomethylation and targets CDKN1A/p21, PTEN, AKT3 and TIMP2., This study identifies a trisomy on chromosome 1q, which encompasses AKT3, and a separate activating AKT3 somatic mutation in patients with the developmental brain disorder hemimegalencephaly., Exome sequencing and mass spectrometry analysis in paired brain-blood samples from individuals with hemimegalencephaly (20 cases) identified de novo somatic mutations in 30% of affected individuals in the PIK3CA, AKT3 and MTOR genes., identified mutations in AKT3, PIK3R2 and PIK3CA in 11 unrelated families with megalencephaly-capillary malformation and megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndromes, AKT3, ANGPTL4, eNOS3, and VEGFA associations with high altitude sickness in Han and Tibetan Chinese at the Qinghai-Tibetan Plateau., AKT isoforms 1 and 3 promote basal as well as EGF-induced trophoblast migration., Akt3 coimmunoprecipitates with Ago2., Duplication of AKT3 causes macrocephaly., Induction of transgenic Akt3 constitutively activates pathways for survival by counteracting motor neuronal degeneration in patients with amyotrophic lateral sclerosis., detected and measured all three AKT isoforms 1, 2 and 3 to enable the study of the multiple and variable roles that these isoforms play in AKT breast tumorigenesis, Various AKT3 mutations are important in neurological disorders, such as microcephaly, hemimegalencephaly, and megalencephaly syndromes, Our study revealed AKT-3 amplification and deletions in 11% (9/82) and 13% (11/82) of triple-negative breast cancers, respectively., Experimental validation indicate that AKT1, AKT2 and AKT3 proteins may all be novel unfavorable prognostic factors for patients with hepatocellular carcinoma., targeting Akt3 and downstream signaling may be an effective approach to inhibit growth of triple-negative breast cancer (TNBC0., IWS1, an RNA processing regulator, is phosphorylated by Akt3 and Akt1 at Ser720/Thr721 in lung cancer, Inactivation of AKT3 in ErbB2+/ERalpha- breast cancer cells results in decreased expression of ErbB2 and ErbB3, but increased expression of ERalpha., miR-489 inhibited cisplatin resistance and cell growth, and promotes apoptosis by suppressing Akt3 expression., miR-145 suppresses thyroid cancer growth and metastasis and targets AKT3, Akt3 is a negative regulator of IGFBP-3 protein., Knockdown of AKT3 and/or PI3KCA genes in T98G cells led to a significant reduction in cell viability, the accumulation of subG1-phase cells and, a reduced fraction of cells in the S and G2/M phases., These findings indicate that AKT3 upregulation may cause focal malformations of cortical development., The PI3K/AKT/mTOR pathway is distinguishable in SCLC genomic alterations. Therefore, a sequencing-based comprehensive analysis could stratify SCLC patients by potential therapeutic targets., Data suggest that three isoforms of the serine/threonine protein kinase Akt (Akt1, Akt2, Akt3) regulate cell survival, cell growth, cell proliferation, and cell metabolism in breast cancer cells. [REVIEW], The individual contribution of each Akt isoform in p120 RasGAP fragment N-mediated cell protection against Fas ligand induced cell death, was investigated., MiR-22 induces EPC senescence by downregulating AKT3 expression., Mechanistic investigations uncovered opposing functions for different Akt isoforms in this regulation, where Akt1 promotes and Akt3 inhibits vascular tumor growth., A 1q44 deletion involving only AKT3 in a boy and his father, is reported., AKT3, PI3KCA, and VEGFR2 silencing reduces the invasiveness of glioblastoma multiforme T98G cells., findings identify PI3K/AKT pathway mutations as an important cause of epileptogenic brain malformations and establish megalencephaly, hemimegalencephaly, and focal cortical dysplasia as part of a single pathogenic spectrum., Akt3-expressing human glioblastoma cells had enhanced activation of DNA repair proteins, leading to increased DNA repair and subsequent resistance to radiation and temozolomide., miR-582-5p regulated the progression of hepatocellular carcinoma through directly inhibiting the expression of CDK1 and AKT3, and indirectly inhibiting the expression of cyclinD1, Flot-2 exerts a pro-neoplastic role in NPC and is involved in tumor progression and metastasis. Moreover, Flot-2 exerts its role through NF-kappaB and PI3K/Akt3 signaling., mirn424 has a role in inhibiting Akt3/E2F3 axis and tumor growth in hepatocellular carcinoma, AKT3 has a role in prostate cancer proliferation through regulation of Akt, B-Raf, and TSC1/TSC2, Data show that both serine/threonine phosphatases PHLPP and dephosphorylated the physiological substrates of Akt1 and Akt3 with similar efficiencies., High AKT3 expression is associated with ovarian cancer., These findings suggest a central AKT-FOXG1-reelin signaling pathway in focal malformations of cortical development and support pathway inhibitors as potential treatments or therapies for some forms of focal epilepsy., Downregulation of AKT3 increases migration and metastasis in triple negative breast cancer cells by upregulating S100A4., Akt1 and Akt2 activated both SREBP-1 and SREBP-2, whereas Akt3 upregulated SREBP-1 to enhance hepatitis C virus translation.,
OMIM_DISEASE Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., domain:Binding of the PH domain to the phosphatidylinositol 3-kinase alpha (PI(3)K) results in its targeting to the plasma membrane., enzyme regulation:Two specific sites, one in the kinase domain (Thr-305) and the other in the C-terminal regulatory region (Ser-472), need to be phosphorylated for its full activation., function:IGF-1 leads to the activation of AKT3, which may play a role in regulating cell survival. Capable of phosphorylating several known proteins. Truncated isoform 2/PKB gamma 1 without the second serine phosphorylation site could still be stimulated but to a lesser extent., PTM:Phosphorylated upon DNA damage, probably by ATM or ATR., similarity:Belongs to the protein kinase superfamily., similarity:Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. RAC subfamily., similarity:Contains 1 AGC-kinase C-terminal domain., similarity:Contains 1 PH domain., similarity:Contains 1 protein kinase domain., subcellular location:Membrane-associated after cell stimulation leading to its translocation., subunit:Interacts (via PH domain) with TCL1A; this enhances AKT3 phosphorylation and activation., tissue specificity:In adult tissues, it is highly expressed in brain, lung and kidney, but weakly in heart, testis and liver. In fetal tissues, it is highly expressed in heart, liver and brain and not at all in kidney.,