Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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AKT serine/threonine kinase 2(AKT2) AKT serine/threonine kinase 2(AKT2) Related Genes Homo sapiens
CYTOBAND 19q13.1-q13.2,
GENERIF_SUMMARY evidence that Akt2 is transcriptionally regulated by MyoD and activates MyoD-myocyte enhancer binding factor-2 (MEF2) transactivation activity, role in inhibiting JNK through activation of NF kappa B pathway in human epithelial cells, In renal tubular epithelial cell, Akt phosphorylation is up-regulated in an effort to minimize cell death., Activation of AKT consequent to binding of albumin by CLL cells blocks chlorambucil- and radiation-induced apoptosis., a new mechanism for androgen-mediated prostate cancer cell survival and establish FKHR as nuclear target for both AKT-dependent and -independent survival signals in prostate cancer cells., Results describe the structure of an inactive and unliganded Akt2 kinase domain, and several features that distinguish it from other kinases., data indicate that AKT2 mediates PI3-K-dependent effects on adhesion, motility, invasion, and metastasis in vivo, These results indicate that PI3k/Akt pathway is involved in the signaling cascade of glioma cells required to induce cell migration., 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, AKT2 sensitizes A2780S and cisplatin-resistant A2780CP cells to cisplatin-induced apoptosis through regulation of the ASK1/JNK/p38 pathway., both p70S6K and Akt are activated in the majority of human papillary cancer cells., Akt regulates basic helix-loop-helix transcription factor-coactivator complex formation and activity during neuronal differentiation, Akt2 phosphorylates MLK3, which results in the disassembly of the JNK complex bound to POSH and down-regulation of the JNK signaling pathway, Akt2 may be an important regulator of both Xiap and p53 contents in ovarian cancer after CDDP challenge., Our data suggest that Akt is an endogenous inhibitor during TRAIL-mediated synovial cell apoptotic pathway., Findings suggest that Akt2 is a novel independent predictor for the development and progression of hepatocellular carcinoma ., Lipid rafts(LR) may play important role in determining function of PI 3-K/Akt2 signaling, including stimulation of intestinal Na absorption. LR-associated Akt2 may be involved in enterocyte differentiation., data suggest that upstream perturbations of the PI3K/AKT pathway contribute to frequent activation of AKT2 in pancreatic cancer, which may contribute to the pathogenesis of this highly aggressive form of human malignancy, Thus a physiological concentration of insulin stimulated Akt-1 & Akt-2 phosphorylation in human skeletal muscle in the absence of hyperglycemia, but Akt-2 expression is impaired in muscle of obese patients with atypical diabetes with severe hyperglycemia., activated Akt and Akt2 have roles in progression of pancreatic ductal adenocarcinoma, These results suggest that cross-talk between the PKB and caspase-8 pathways may regulate the balance between cell survival and cell death in ECV304., a mutation in AKT2 in a family showing autosomal dominant inheritance of severe insulin resistance and diabetes mellitus is described; the mutant kinase in cultured cells disrupted insulin signaling and inhibited the function of coexpressed, wild-type AKT, Akt2 is a critical kinase that regulates ezrin phosphorylation and activation, AKT2 plays an important role in glioma cell motility and invasion, Kinetic analysis of GST-AKT2 demonstrates that phosphorylation of Thr309 in the activation loop of the kinase is largely responsible for observed reduction in Km & for a subsequent 150-fold increase in the catalytic efficiency (k(cat)/Km) of the enzyme., in breast cancer patients, Akt activation is associated with tumour proliferation and poor prognosis, particularly in the subset of patients with ErbB2-overexpressing tumours, In this study, we provide evidence for isoform-specific positive and negative roles for Akt1 and -2 in regulating growth factor-stimulated phenotypes in breast epithelial cells, results suggest that AKT pathway may play an important role in the development and progression of gliomas, These data show that specific interaction of the Akt2 isoform with p21 is key to its negative effect on normal cell cycle progression., Akt1 and Akt2 have opposing roles in Rac/Pak signaling and cell migration, Akt1 induces CREB phosphorylation at Ser-133 and CREB target gene expression., Sequencing of the entire coding region and splice junctions of AKT2 and the relationship of genetic variations in the gene with multiple metabolic diseases is reported., Twist as a positive transcriptional regulator of AKT2 expression; Twist-AKT2 signaling is involved in promoting invasive ability and survival of breast cancer cells., Changes in tissue pressure during inflammation may regulate macrophage phagocytosis by activation of PI-3K, which activates Akt2, mTOR, and p70S6K., the PI3K/AKT/mTOR signaling pathway is involved in regulation of SphK1, with AKT2 playing a key role in PDGF-induced SphK1 expression, Two variants in 5' regulatory region of Akt2 gene are associated and may modulate susceptibility to insulin resistance and related metabolic abnormalities., AKT2 up-regulation is characteristic of skin squamous cell carcinoma and coincident AKT2 activation through serine phosphorylation correlates with malignancy., Pressure did not stimulate translocation of AKT2 to the plasma membrane., PKB[alpha] and/or PKB[gamma] and not PKB[beta] alone are involved in gemcitabine resistance mechanisms., Akt2 is required for rapamycin-induced vascular smooth muscle cell differentiation, whereas Akt1 appears to oppose contractile protein expression., Akt1 and Akt2 mediate GPIb-IX signaling via the cGMP-dependent signaling pathway., a key regulatory role of the Akt/mTOR pathway in the generation of the effects of As(2)O(3), Functional convergence of Twist and AKT2 underscores the importance of this signaling pathway in tumor development and progression., Dlx5 can act as an oncogene by cooperating with Akt2 to promote lymphomagenesis, Results suggest that Akt2 directly mediates EGF-induced chemotactic signaling pathways through PKCzeta and its expression is critical during the extravasation of circulating cancer cells., Polymorphisms in two components of the insulin signaling pathway, AKT2 and GSK3B, are associated with polycystic ovary syndrome., Akt2 down-regulation sensitizes ovarian cancer cells to paclitaxel-induced apoptosis, and inhibits survivin expression, an important role of PKC-delta and PI3K/Akt1,2 pathways in activating mTOR as an endogenous modulator to ensure a tight regulation of NF-kappaB signaling of ICAM-1 expression in endothelial cells., the consequence of PTEN loss and Akt2 overexpression function synergistically to promote metastasis, mtDNA depletion prevents detachment-induced apoptosis (anoikis) and promotes migratory capabilities onto basement membrane proteins through upregulation of p85 and p110 phosphatidylinositol 3-kinase (PI3K) subunits, which results in Akt2 activation, Akt2 up-regulates beta1 integrins & promotes adhesion & invasion of breast cancer cells in vitro & also metastasis in vivo. It opposes Akt1. Review., genetic variations in akt2 were associated with survival in esophageal cancer, Akt2 plays an essential role in both CSF-1- and chemokine-induced chemotaxis of macrophages., 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., The positive rate of AKT2 protein expression in laryngeal squamous cell carcinoma was significantly higher than that in peri-cancer tissue and normal laryngeal epithelium, and was correlated with tumor site, lymph node metastasis and clinical stage., mTOR/Akt2 is required for optimal PPARgamma activation. Patients who receive SESs during concomitant RSG treatment may be at risk for delayed stent healing., induction of EMT is controlled by microRNAs whose abundance depends on the balance between Akt1 and Akt2 rather than on the overall activity of Akt, Taken together, these results showed that, in addition to the MAPK pathway previously reported being a downstream target of stimulated Grm1, AKT2 is another downstream target in Grm1 mediated melanocyte transformation., These findings provide further evidence of the importance of mediators of the growth factor signaling in ER regulation, introducing the Akt2/FoxO3a axis as a pursuable target in therapy for ER-positive breast cancer., Akt2 was located in the mitochondria of human cell lines., Plasmin triggers chemotaxis of monocyte-derived dendritic cells through an Akt2-dependent pathway and promotes a T-helper type-1 response., By using yeast two-hybrid systems with full-length human Akt2 as bait, we found a stable interaction between the tetratricopeptide (TPR) repeat domain 3 (TTC3) and Akt; finding could underlie important clinical manifestations of Down syndrome., In breast cancer AKT3 amplifications and AKT1 and AKT2 deletions were seen by FISH, Results represent the first indication that Akt isoforms regulate intermediate filament protein expression and support the hypothesis that IFs are involved in PI3K/Akt pathway., Akt2 may play a critical role in the development of gliomas and present a potential therapeutic target for malignant gliomas, Data show that AKT1 and AKT2 appeared to regulate growth through FOXO proteins, but not through either GSK3beta or mTOR, and in contrast, inactivation of PDPK1 affected GSK3beta and mTOR activation., 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, AKT2 mutation coexisted with EGFR and PIK3CA mutations was associated with lung cancer., Studies indicate that three different isoforms Akt1, Akt2, and Akt3 have distinct expression patterns and functions., MYCN contributes to tumorigenesis, in part, by repressing miR-184, leading to increased levels of AKT2, a direct target of miR-184, AKT2 expression is associated with more advanced and especially aggressive gliomas and critical for cell survival and invasion., SGK3 is not required for insulin-induced PFK-2 activation and that this effect is likely mediated by PKBalpha., The expression levels and activities of exogenous Akt1 and Akt2 are almost identical, Akt2 exerted a greater inhibitory effect on both proliferation and cell migration., The positive expression of p-AKT2 in lung adenocarcinoma was higher than that in lung squamous carcinomas., Akt signaling regulates the stability of palladin, Expressions of Akt1, Akt2 and PI3K were decreased in ovarian epithelial cancer cells transduced with PTEN., Advanced glycation end products of BSA can induce endothelial-to-mesenchymal transition of cultured human and monkey endothelial cells and AKT2 may play a role in this process., Data suggest that Akt2/B23 functions as an oncogenic unit to drive tumorigenesis of A549 lung cancer cells., Akt2 augments cell proliferation by facilitating cell cycle progression through the upregulation of the cell cycle engine, and protects a cell from pathological autophagy by modulating mitochondrial homeostasis., analysis of the roles of Akt1 and Akt2 in cancer [review], loss of Akt1 or Akt2 decreased proliferation of Pten wild-type astrocytes, whereas combined loss of multiple isoforms was needed to inhibit proliferation of Pten-null astrocytes, The Akt2 gene is not a major cause of diabetes in a non-obese Chinese Han population characterized by insulin resistance., Transcriptional activation of the Akt2 pathway indicates that it is involved in lumbar disc degeneration., Data suggest a regulation pathway of B-cell-lymphoma-2 (Bcl-2) by cisplatin, via the activation of PKC and Akt2, which has impact on resistance to cisplatin-induced apoptosis in endometrial cancer cells., High AKT2 is associated with glioma progression., Angiopoietin-2, an angiogenic regulator, promotes initial growth and survival of breast cancer metastases to the lung through the integrin-linked kinase (ILK)-AKT1,2-B cell lymphoma 2 (Bcl-2) pathway., AKT1 and AKT2 both contribute to cell survival, albeit via different mechanisms; the effects on cell growth and migration are predominantly regulated by AKT1, This study revealed a novel mechanism of Akt2 regulation by ErbB2 in prostate cancer cells., 3 unrelated children with unexplained, recurrent and severe fasting hypoglycemia and asymmetrical growth were found to carry the same de novo mutation, p.Glu17Lys, in AKT2, in 2 cases as heterozygotes and in 1 case in mosaic form, Akt2 kinase suppresses glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-mediated apoptosis in ovarian cancer cells via phosphorylating GAPDH at threonine 237 and decreasing its nuclear translocation, analysis of resistance of Akt kinase and PP2A to dephosphorylation through ATP-dependent conformational plasticity, 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., Unexpected roles of Akt2 in transcriptional control and phosphorylation of Thr45 in histone H3 as a new epigenetic mark related to Snail1 and Akt2 action., Akt2 is a negative regulator of NFAT activation through its ability to inhibit calcium mobilization from the endoplasmic reticulum., study concludes that Akt2 is indispensable for the regulation of preadipocyte and adipocyte number, whereas Akt1 and Akt2 are equally important for the regulation of insulin-stimulated metabolic pathways in adipocytes, Although there is an association of PI3 kinase signaling and chemoresistance in advanced ovarian cancer, there is no clear evidence that this is driven specifically by AKT2 mutations., amplification of AKT1 and/or AKT2 and high-level polysomy were found in 16% of total lung carcinoma cases, and this defined subset was characterized by the overexpression/activation of Akt, reciprocal to EGFR aberrations., In transfected HEK2 cells, basal activity of Akt2 regulates DAT cell surface expression., these data define an inhibitory role for both AKT1 and AKT2 in prostate cancer migration and invasion and highlight the cell type-specific actions of AKT kinases in the regulation of cell motility., An Akt2/PKBbeta-targeted siRNA inhibited the 8-Cl-cAMP- and AICAR-mediated phosphorylation of AMPK and p38 MAPK., CD40L-provoked signaling results in the production of several cytokines. Among these, IL-6 expression is mediated through Akt and NF-kappaB pathways., In cultured human aortic vascular smooth muscle cells, AKT2 inhibited the expression of MMP-9 and stimulated the expression of TIMP-1 by preventing the binding of transcription factor forkhead box protein O1 to the MMP-9 and TIMP-1 promoters., Data indicate that the prognostic value of Akt2 increases with higher oestrogen receptor (ER) expression, motivating further mechanistic studies on the role of Akt2 in ER+ breast cancer., Data suggest that although COOH-terminal dephosphorylation is likely necessary for glycogen synthase (GS) activation, Akt2-dependent NH2-terminal dephosphorylation is the site for "fine-tuning" insulin-mediated GS activation in skeletal muscle., Insulin signaling via Akt2 switches plakophilin 1 function from stabilizing cell adhesion to promoting cell proliferation., In a manner that depended on the level of phosphorylated AKT1/2 protein., Akt2 regulates metastatic potential in neuroblastoma., AKT1 and AKT2 have non-redundant roles in the regulation of prostate cancer cell proliferation and migration., Depletion of both Akt2 and ASAH1 is much more potent than depleting each alone at inhibiting neoplastic cell viability/proliferation and invasion., Findings suggest an important role of Gli1 as a tumor suppressor in neuroblastoma, and offer a mechanism by which AKT2 regulates the subcellular localization, and in turn, inhibits the tumor-suppressive function of Gli1 in neuroblastoma., 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, overexpression of 4EBP1, p70S6K, Akt1 or Akt2 could promote the Coxsackievirus B3-induced apoptosis., AKT2 is closely linked to Type II diabetes and the implications of various types of mutations are discussed, results disclose a new function of Akt2 and identify a potential therapeutic target for preserving glomerular function in CKD, Akt2 downregulation favors limbal keratinocyte stem cell maintenance as a result of a gain of FOXO functions., Knockdown of RPS7 resulted in increased expression of P85alpha, P110alpha, and AKT2., Experimental validation indicate that AKT1, AKT2 and AKT3 proteins may all be novel unfavorable prognostic factors for patients with hepatocellular carcinoma., in a defined subset of bone and soft tissue tumors, including benign tumors, Akt was frequently overexpressed and activated, and AKT1/2 copy number was increased, Results show that miR-302b inhibits hepatocellular carcinoma cell proliferation and growth in vitro and in vivo by targeting AKT2., AA induces Akt2 activation and invasion in MDA-MB-231 cells. Akt2 activation requires the activity of Src, EGFR, and PIK3, whereas migration and invasion require Akt, PI3K, EGFR and metalloproteinases activity., AKT2 inhibition reduced heterotypic aggregation of neutrophils and platelets isolated from sickle cell disease patients, suggesting that AKT2 is important for neutrophil recruitment and neutrophil-platelet interactions., AKT2 may play an important role in the development of meningioma. High AKT2 labeling index indicates higher grade of meningioma, and therefore AKT2 may be a useful molecular marker for predicting the prognosis of meningioma., We examined the response of 80 samples of primary cells from acute myeloid leukemia patients to selective inhibitors of the phosphatidylinositol 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) axis., CK2-dependent phosphorylation is therefore a crucial event which, discriminating between Akt1 and Akt2, can account for different substrate specificities., SchA-FAK-p85 complex subsequently selectively recruited and activated Akt2, not Akt1, The specific role of AKT2 in tumor maintenance provides a rationale for the development of isoform-specific inhibitors for patients with PTEN-deficient cancers., Findings suggest that adding chloroquine to EGF receptor (EGFR) and AKT2 inhibition has the potential to improve tumor responses in EGFR M+ non-small cell lung cancer (NSCLC)., Findings indicate that miR-137 is a valuable biomarker for hepatocellular carcinoma (HCC) prognosis and the forkhead box D3 (FoxD3)/miR-137/AKT2 regulatory network plays an important role in HCC progression., Role of the guanine nucleotide exchange factor in Akt2-mediated plasma membrane translocation of GLUT4 in insulin-stimulated skeletal muscle., Knockdown of Akt2 using siRNAs or the PI3K inhibitor Ly294002 inhibited TGF-beta1-induced phosphorylation of GSK3beta and expression of Snail1, the biological effect of Akt2 in colorectal cancer cells, AKT isoform-specific knock down combined with quantitative phosphoproteomics provided a powerful strategy to unravel AKT isoform-specific signaling, Mutations in genes such as AKT2, CCNA1, MAP3K4, and TGFBR1, were associated significantly with Epstein-Barr-positive gastric tumors, compared with EBV-negative tumors., 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., Akt1 and Akt2 are involved in albumin endocytosis, and phosphorylation of Dab2 by Akt induces albumin endocytosis in proximal tubule epithelial cells., MiR-194 deregulation contributes to colorectal carcinogenesis via reducing the expression AKT2., let-7b/g inhibited AKT2 expression by directly binding to its 3'UTR, reduced p-AKT (S473) activation and suppressed expression of the downstream effector pS6., Our study uncovers a novel molecular mechanism by which AEG-1 augments glioma progression and offers a rationale to block AEG-1-Akt2 signaling function as a novel GBM treatment., findings suggested that AKT2 may be one of the targets of miR29s in gastric cancer, The results indicate that BCAM-AKT2 expression is a new mechanism of AKT2 kinase activation in high-grade serous ovarian carcinoma., PIK3CA and AKT2 mutations occurred at low frequency in gastric cancer., miR-615-5p inhibits pancreatic cancer cell proliferation, migration, and invasion by targeting AKT2, we assayed expression of myosin II.. this assay is a powerful predictor of the use of ZEB2/Akt2 as a marker for tumor progression in serous ovarian cancers., QSAR based docking studies identify marine algal callophycin A as inhibitor of protein kinase B beta., Up-regulation of AKT2 was associated with chemoresistance in renal cell carcinoma., miR-137 which is frequently down-regulated in gastric cancer is potentially involved in gastric cancer tumorigenesis and metastasis by regulating AKT2 related signal pathways, miR-612 directly suppressed AKT2, which in turn inhibited the downstream epithelial-mesenchymal transition-related signaling pathway., the correlation between RLN2 and p-AKT or RLN2 and p-ERK1/2 expression was investigated., Combined PI3K/Akt and Hsp90 targeting synergistically suppresses essential functions of alloreactive T cells and increases Tregs., AKT1 but not AKT2 protects islet cells from apoptosis and drives proliferation., High constitutive Akt2 activity in U937 promonocytes, These studies identify Akt2 as a critical kinase that regulates radixin phosphorylation and leads to Mrp-2 translocation and function., High AKT2 expression is associated with ovarian cancer., Active, phosphorylated Akt2 translocates to the nucleus in Notch-expressing cells, resulting in GSK-3beta inactivation in this compartment., Akt1 and Akt2 activated both SREBP-1 and SREBP-2, whereas Akt3 upregulated SREBP-1 to enhance hepatitis C virus translation., controls endothelial Jagged1 expression and, thereby, Notch signalling regulating VSMC maintenance.,
OMIM_DISEASE Diabetes mellitus, type II, Hypoinsulinemic hypoglycemia with hemihypertrophy,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., disease:Alterations of AKT2 may contribute to the pathogenesis of ovarian carcinomas., enzyme regulation:Two specific sites, one in the kinase domain (Thr-309) and the other in the C-terminal regulatory region (Ser-474), need to be phosphorylated for its full activation., function:General protein kinase capable of phosphorylating several known proteins., 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., subunit:Interacts (via PH domain) with MTCP1, TCL1A AND TCL1B., tissue specificity:In all human cell types so far analyzed.,