AKT2 (v-akt murine thymoma viral oncogene homolog 2)

2007-07-01   Deborah A. Altomare , Joseph R. Testa 

Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA

Identity

HGNC
LOCATION
19q13.2
IMAGE
Atlas Image
LOCUSID
ALIAS
HIHGHH,PKBB,PKBBETA,PRKBB,RAC-BETA
FUSION GENES

DNA/RNA

Atlas Image
Genomic organization of human AKT2. Open boxes indicate untranslated regions and shaded boxes indicate coding regions of the gene. The ATG transcription start site is located in exon 2 and the TGA termination codon is located in exon 14.

Description

The entire gene is about 54.4 Kb and contains 14 exons. The open reading frame of the coding region is 1,445 bp.

Transcription

Transcript length: 4,623 bp

Pseudogene

No human pseudogene known. A mouse Akt2 pseudogene was cloned and mapped to proximal mouse chromosome 11 by fluorescence in situ hybridization.

Proteins

Atlas Image
AKT proteins contain an amino terminal pleckstrin homology (PH) domain, followed by a short helical region and kinase domain that terminates in a regulatory hydrophobic motif. Activation of AKT kinases is a multi-step process that involves both membrane translocation and phosphorylation. AKT activation occurs by means of stimulation of the growth factor receptor-associated phosphatidylinositol 3-kinase (PI3K). PI3K generates 3-phosphorylated phosphoinositides, i.e., phosphatidylinositol-3,4,5-trisphosphate (PIP3) and phosphatidylinositol-3,4-bisphosphate (PIP2) at the plasma membrane. Both phospholipids bind with high affinity to the PH domain, mediating membrane translocation of AKT. At the membrane, AKT2 is phosphorylated at two sites, threonine 309 (T309) and serine 474 (S474).

Description

AKT2 protein consists of 481 amino acids, with a molecular weight of 55,769 Da.

Expression

Found in all human cell types so far analyzed; insulin responsive tissues such as normal brown fat, skeletal muscle and liver exhibit the highest expression levels of AKT2/Akt2.

Localisation

Predominantly cytoplasmic; also found at the plasma membrane and in the nucleus following its activation.

Function

AKT proteins mediate a variety of cellular functions, ranging from control of cell proliferation and survival to modulation of intermediary metabolism and angiogenesis. Such pleiotropic effects are the consequence of phosphorylation of numerous substrates, some of which are listed below. Most substrates share the consensus sequence for AKT phosphorylation, RXRXXS/T. For example, activated AKT exerts anti-apoptotic activity in part by preventing the release of cytochrome c from mitochondria, and phosphorylating and inactivating the pro-apoptotic factors BAD and pro-caspase-9. AKT also activates IkappaB kinase (IKK), a positive regulator of NF-kappaB, which results in the transcription of anti-apoptotic genes. AKT phosphorylates and inactivates FOXO transcription factors, which mediate the expression of genes critical for apoptosis, such as the Fas ligand gene.
AKT activation mediates cell cycle progression by phosphorylation and inhibition of glycogen synthase kinase 3 beta to inhibit cyclin D1 degradation. AKT phosphorylates the cell cycle inhibitors p21WAF1 and p27Kip1 near the nuclear localization signal to induce cytoplasmic retention of these cell cycle inhibitors. Moreover, phosphorylation of AKT kinases also results in increased translation of cyclin D1, D3 and E transcripts.
AKT activates the downstream mTOR kinase by inhibiting a complex formed by the tumor suppressor proteins TSC1 and TSC2, also known as hamartin and tuberin, respectively. mTOR broadly mediates cell growth and proliferation by regulating ribosomal biogenesis and protein translation and can regulate response to nutrients by restricting cell cycle progression in the presence of suboptimal growth conditions.
AKT signaling also contributes to other cellular processes considered to be cancer hallmarks. AKT promotes the phosphorylation and translocation of Mdm2 into the nucleus, where it downregulates p53 and thereby antagonizes p53-mediated cell cycle checkpoints. AKT signaling is linked to tumor cell migration, and it contributes to tumor invasion and metastasis by promoting the secretion of matrix metalloproteinases. Moreover, vascular endothelial growth factor (VEGF) effects on cell survival have been shown to be mediated by the Flk1/VEGFR2-PI3K-AKT pathway. In other cellular processes, AKT has been shown to phosphorylate human telomerase reverse transcriptase (hTERT), thereby stimulating telomerase activity and replication. Collectively, these findings implicate up-regulation of the AKT pathway in many aspects of tumorigenesis.

Homology

All three AKT kinases belong to the more general class of AGC kinases (related to AMP/GMP kinase and protein kinase C). The kinase domain of AKT shares high similarity with other members of the AGC family of kinases such as PKA, PKC, p70 S6K, and p90 RSK. The sequence identities among the three AKTs in the kinase domain exceed 87%. The three AKT kinases are identical in the ATP binding region, except for one residue: Ala 230 of AKT1 is conserved in AKT2 (Ala 232), but switches to Val 228 in AKT3. In addition, each of the three AKT kinases has a carboxy terminal extension of about 40 amino acids.
Human AKT2 is 98.1% similar to M. musculus Akt2; 97.7% similar to the R. norvegicus homolog; 61.3% similar to D. melanogaster protein kinase RAC; 52.4% similar to C. elegans Akt/PKB serine/threonine kinase; 47.7% similar to S. cerevisiae protein kinase (see UniGene Hs.631535)

Mutations

Germinal

Insulin resistance and a diabetes mellitus-like syndrome have been described in knockout mice lacking Akt2.

Somatic

Individuals carrying a G-to-A transition in the AKT2 gene resulting in an Arg-to-His substitution at codon 274 (R274H) were found to be markedly hyperinsulinemic. However, a large case-control study showed that variation in and around the AKT2 locus is unlikely to contribute significantly to increased risk of type 2 diabetes.
Mutations in AKT2 are uncommon in human tumors. For example, AKT2 mutations have been reported in 1 of 51 gastric carcinomas and 2 of 79 lung carcinomas. The mutations consisted of one missense mutation and 2 splice site mutations in an intron.

Implicated in

Entity name
Various cancers
Prognosis
Frequent activation of AKT has been reported in a broad range of human cancers including various carcinomas, glioblastoma multiforme, and hematological malignancies. In some of these tumor types, AKT activation has been shown to correlate with advanced disease and/or poor prognosis. AKT is a major mediator of survival signals that protect cells from undergoing apoptosis and, thus, is a potentially important therapeutic target. Ovarian cancer cell lines with either constitutive AKT1 activity or AKT2 gene amplification have been shown to be highly resistant to paclitaxel compared to cells with low AKT levels.
Atlas Image
Hyperactivation of AKT kinases have been reported in a wide assortment of human solid tumors and hematological malignancies. Activation of growth factor receptors either by ligand stimulation or receptor overexpression/mutation is one of the mechanisms leading to the upregulation of AKT signaling. Other mechanisms include activation of oncoproteins and inactivation of tumor suppressors intersecting the AKT signal transduction pathway. AKT is now known to be a central player in a signaling pathway consisting of many components that have been implicated in tumorigenesis, including upstream phosphatidylinositol 3-kinase (PI3K) and PTEN (Phosphatase and Tensin homologue deleted on chromosome Ten). Several proteins, such as AKT, eIF4E, and the subunits of PI3K, can act as oncoproteins when activated or overexpressed. Germline mutations in PTEN, LKB1, TSC2/TSC1, and VHL are linked with different dominantly-inherited cancer syndromes. Each of these tumor suppressors is a negative regulator of the AKT pathway which, when deregulated, results in altered translation of cancer-related mRNAs that regulate cellular processes such as cell cycle progression, growth, cell survival, invasion, and communication with the extracellular environment.
Oncogenesis
In 1992, amplification and overexpression of AKT2 was reported in a subset of ovarian carcinomas. AKT2 was shown to be amplified and overexpressed in 2 of 8 ovarian carcinoma cell lines and 2 of 15 primary ovarian tumors. Recently, amplification of AKT2 was found in 18.2% of high-grade ovarian carcinomas.
Amplification and/or overexpression of AKT2 was reported in 10-20% of primary pancreatic carcinomas and pancreatic cancer cell lines. PANC1 and ASPC1 cell lines exhibited 30-fold and 50-fold amplification of AKT2, respectively, and highly elevated levels of AKT2 RNA and protein. As an early indication of the potential importance of molecularly targeting the AKT pathway, AKT2 expression and tumorigenicity of PANC1 cells in nude mice was markedly inhibited by transfection with an antisense AKT2 construct but not with a control AKT2 construct in the sense orientation. Through the use of in vitro kinase assays, activation of the AKT2 kinase has been observed in about 40% of ovarian and pancreatic cancers.

Bibliography

Pubmed IDLast YearTitleAuthors
162882922005Perturbations of the AKT signaling pathway in human cancer.Altomare DA et al
162882942005Tuberous sclerosis complex: linking growth and energy signaling pathways with human disease.Astrinidis A et al
160959992005Activation of AKT kinases in cancer: implications for therapeutic targeting.Bellacosa A et al
14096331992AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas.Cheng JQ et al
86229881996Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA.Cheng JQ et al
113874802001Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta).Cho H et al
152093772004PI 3-kinase, Akt and cell survival.Downward J et al
151663802004A family with severe insulin resistance and diabetes due to a mutation in AKT2.George S et al
106479312000The hallmarks of cancer.Hanahan D et al
114103352001Expression, purification, characterization and homology modeling of active Akt/PKB, a key enzyme involved in cell survival signaling.Kumar CC et al
158003332005Possible future issues in the treatment of glioblastomas: special emphasis on cell migration and the resistance of migrating glioblastoma cells to apoptosis.Lefranc F et al
128514862003Multiple roles of the PI3K/PKB (Akt) pathway in cell cycle progression.Liang J et al
105938571999Studies of the molecular mechanisms in the regulation of telomerase activity.Liu JP et al
122175212002The PTEN, Mdm2, p53 tumor suppressor-oncoprotein network.Mayo LD et al
87807191996Isolation of DNA sequences amplified at chromosome 19q13.1-q13.2 including the AKT2 locus in human pancreatic cancer.Miwa W et al
97927031998Cyclin D expression is controlled post-transcriptionally via a phosphatidylinositol 3-kinase/Akt-dependent pathway.Muise-Helmericks RC et al
167210432006Sequence mutations and amplification of PIK3CA and AKT2 genes in purified ovarian serous neoplasms.Nakayama K et al
107696882000Overexpression of Akt/AKT can modulate chemotherapy-induced apoptosis.Page C et al
162882902005Akt-dependent transformation: there is more to growth than just surviving.Plas DR et al
150771552004Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks.Pommier Y et al
94969071998Amplification and overexpression of the AKT2 oncogene in a subset of human pancreatic ductal adenocarcinomas.Ruggeri BA et al
162882892005The Akt of translational control.Ruggero D et al
120890612002Role of Akt signaling in vascular homeostasis and angiogenesis.Shiojima I et al
170473972006Mutational analysis of AKT1, AKT2 and AKT3 genes in common human carcinomas.Soung YH et al
173274412007Analysis of genetic variation in Akt2/PKB-beta in severe insulin resistance, lipodystrophy, type 2 diabetes, and related metabolic phenotypes.Tan K et al
115729542001AKT plays a central role in tumorigenesis.Testa JR et al
114677752000Fibronectin activates matrix metalloproteinase-9 secretion via the MEK1-MAPK and the PI3K-Akt pathways in ovarian cancer cells.Thant AA et al
151101882004Regulation of sensitivity to TRAIL by the PTEN tumor suppressor.Whang YE et al
108223832000Frequent activation of AKT2 and induction of apoptosis by inhibition of phosphoinositide-3-OH kinase/Akt pathway in human ovarian cancer.Yuan ZQ et al

Other Information

Locus ID:

NCBI: 208
MIM: 164731
HGNC: 392
Ensembl: ENSG00000105221

Variants:

dbSNP: 208
ClinVar: 208
TCGA: ENSG00000105221
COSMIC: AKT2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000105221ENST00000311278P31751
ENSG00000105221ENST00000358335A0A0A0MRF1
ENSG00000105221ENST00000391844J3KT31
ENSG00000105221ENST00000392037A8MX96
ENSG00000105221ENST00000392038P31751
ENSG00000105221ENST00000416362A0A1B0GXA2
ENSG00000105221ENST00000416994C9J258
ENSG00000105221ENST00000423127C9JIJ1
ENSG00000105221ENST00000424901P31751
ENSG00000105221ENST00000427375C9JIF6
ENSG00000105221ENST00000441941C9JHS6
ENSG00000105221ENST00000452077E7EVP8
ENSG00000105221ENST00000456441C9JC83
ENSG00000105221ENST00000476247J3QL45
ENSG00000105221ENST00000486368J3QLS6
ENSG00000105221ENST00000489375M0QZW8
ENSG00000105221ENST00000491778J3KTP4
ENSG00000105221ENST00000492463J3KT31
ENSG00000105221ENST00000497948M0R283
ENSG00000105221ENST00000578123J3KRI8
ENSG00000105221ENST00000578310J3KTC6
ENSG00000105221ENST00000578615J3QKW1
ENSG00000105221ENST00000579047M0R0P9
ENSG00000105221ENST00000580747C9J258
ENSG00000105221ENST00000583859J3KSY8
ENSG00000105221ENST00000584288J3KT31
ENSG00000105221ENST00000596634M0QZK3
ENSG00000105221ENST00000601166M0R275

Expression (GTEx)

0
10
20
30
40
50
60
70
80
90
100

Pathways

PathwaySourceExternal ID
MAPK signaling pathwayKEGGko04010
ErbB signaling pathwayKEGGko04012
Autophagy - animalKEGGko04140
mTOR signaling pathwayKEGGko04150
ApoptosisKEGGko04210
VEGF signaling pathwayKEGGko04370
Focal adhesionKEGGko04510
Toll-like receptor signaling pathwayKEGGko04620
Jak-STAT signaling pathwayKEGGko04630
T cell receptor signaling pathwayKEGGko04660
B cell receptor signaling pathwayKEGGko04662
Fc epsilon RI signaling pathwayKEGGko04664
Insulin signaling pathwayKEGGko04910
Progesterone-mediated oocyte maturationKEGGko04914
Adipocytokine signaling pathwayKEGGko04920
Colorectal cancerKEGGko05210
Renal cell carcinomaKEGGko05211
Pancreatic cancerKEGGko05212
Endometrial cancerKEGGko05213
GliomaKEGGko05214
Prostate cancerKEGGko05215
MelanomaKEGGko05218
Chronic myeloid leukemiaKEGGko05220
Acute myeloid leukemiaKEGGko05221
Small cell lung cancerKEGGko05222
Non-small cell lung cancerKEGGko05223
MAPK signaling pathwayKEGGhsa04010
ErbB signaling pathwayKEGGhsa04012
Autophagy - animalKEGGhsa04140
mTOR signaling pathwayKEGGhsa04150
ApoptosisKEGGhsa04210
VEGF signaling pathwayKEGGhsa04370
Focal adhesionKEGGhsa04510
Toll-like receptor signaling pathwayKEGGhsa04620
Jak-STAT signaling pathwayKEGGhsa04630
T cell receptor signaling pathwayKEGGhsa04660
B cell receptor signaling pathwayKEGGhsa04662
Fc epsilon RI signaling pathwayKEGGhsa04664
Insulin signaling pathwayKEGGhsa04910
Adipocytokine signaling pathwayKEGGhsa04920
Pathways in cancerKEGGhsa05200
Colorectal cancerKEGGhsa05210
Renal cell carcinomaKEGGhsa05211
Pancreatic cancerKEGGhsa05212
Endometrial cancerKEGGhsa05213
GliomaKEGGhsa05214
Prostate cancerKEGGhsa05215
MelanomaKEGGhsa05218
Chronic myeloid leukemiaKEGGhsa05220
Acute myeloid leukemiaKEGGhsa05221
Small cell lung cancerKEGGhsa05222
Non-small cell lung cancerKEGGhsa05223
Chemokine signaling pathwayKEGGko04062
Chemokine signaling pathwayKEGGhsa04062
Neurotrophin signaling pathwayKEGGko04722
Neurotrophin signaling pathwayKEGGhsa04722
Fc gamma R-mediated phagocytosisKEGGko04666
Fc gamma R-mediated phagocytosisKEGGhsa04666
Progesterone-mediated oocyte maturationKEGGhsa04914
Chagas disease (American trypanosomiasis)KEGGko05142
Chagas disease (American trypanosomiasis)KEGGhsa05142
ToxoplasmosisKEGGko05145
ToxoplasmosisKEGGhsa05145
Carbohydrate digestion and absorptionKEGGko04973
Carbohydrate digestion and absorptionKEGGhsa04973
Hepatitis CKEGGko05160
Hepatitis CKEGGhsa05160
Osteoclast differentiationKEGGko04380
Osteoclast differentiationKEGGhsa04380
MeaslesKEGGko05162
MeaslesKEGGhsa05162
TuberculosisKEGGko05152
TuberculosisKEGGhsa05152
Influenza AKEGGko05164
Influenza AKEGGhsa05164
Cholinergic synapseKEGGhsa04725
HTLV-I infectionKEGGko05166
HTLV-I infectionKEGGhsa05166
Dopaminergic synapseKEGGko04728
Dopaminergic synapseKEGGhsa04728
Epstein-Barr virus infectionKEGGhsa05169
Epstein-Barr virus infectionKEGGko05169
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
Hepatitis BKEGGhsa05161
HIF-1 signaling pathwayKEGGhsa04066
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Estrogen signaling pathwayKEGGhsa04915
Estrogen signaling pathwayKEGGko04915
TNF signaling pathwayKEGGhsa04668
TNF signaling pathwayKEGGko04668
Prolactin signaling pathwayKEGGhsa04917
Prolactin signaling pathwayKEGGko04917
Non-alcoholic fatty liver disease (NAFLD)KEGGhsa04932
Non-alcoholic fatty liver disease (NAFLD)KEGGko04932
Ras signaling pathwayKEGGhsa04014
Rap1 signaling pathwayKEGGhsa04015
Rap1 signaling pathwayKEGGko04015
Adrenergic signaling in cardiomyocytesKEGGhsa04261
Adrenergic signaling in cardiomyocytesKEGGko04261
FoxO signaling pathwayKEGGhsa04068
Thyroid hormone signaling pathwayKEGGhsa04919
Platelet activationKEGGhsa04611
cGMP-PKG signaling pathwayKEGGhsa04022
cGMP-PKG signaling pathwayKEGGko04022
AMPK signaling pathwayKEGGhsa04152
AMPK signaling pathwayKEGGko04152
cAMP signaling pathwayKEGGhsa04024
cAMP signaling pathwayKEGGko04024
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
Central carbon metabolism in cancerKEGGhsa05230
Choline metabolism in cancerKEGGhsa05231
Central carbon metabolism in cancerKEGGko05230
Choline metabolism in cancerKEGGko05231
PI3K-Akt signalingKEGGhsa_M00676
PI3K-Akt signalingKEGGM00676
Sphingolipid signaling pathwayKEGGhsa04071
Glucagon signaling pathwayKEGGhsa04922
Sphingolipid signaling pathwayKEGGko04071
Glucagon signaling pathwayKEGGko04922
Regulation of lipolysis in adipocytesKEGGhsa04923
DiseaseREACTOMER-HSA-1643685
Diseases of signal transductionREACTOMER-HSA-5663202
PI3K/AKT Signaling in CancerREACTOMER-HSA-2219528
Constitutive Signaling by AKT1 E17K in CancerREACTOMER-HSA-5674400
Immune SystemREACTOMER-HSA-168256
Adaptive Immune SystemREACTOMER-HSA-1280218
Costimulation by the CD28 familyREACTOMER-HSA-388841
CD28 co-stimulationREACTOMER-HSA-389356
CD28 dependent PI3K/Akt signalingREACTOMER-HSA-389357
CTLA4 inhibitory signalingREACTOMER-HSA-389513
Signaling by the B Cell Receptor (BCR)REACTOMER-HSA-983705
Downstream signaling events of B Cell Receptor (BCR)REACTOMER-HSA-1168372
PIP3 activates AKT signalingREACTOMER-HSA-1257604
AKT phosphorylates targets in the cytosolREACTOMER-HSA-198323
AKT phosphorylates targets in the nucleusREACTOMER-HSA-198693
Negative regulation of the PI3K/AKT networkREACTOMER-HSA-199418
Innate Immune SystemREACTOMER-HSA-168249
DAP12 interactionsREACTOMER-HSA-2172127
DAP12 signalingREACTOMER-HSA-2424491
Fc epsilon receptor (FCERI) signalingREACTOMER-HSA-2454202
Role of LAT2/NTAL/LAB on calcium mobilizationREACTOMER-HSA-2730905
HemostasisREACTOMER-HSA-109582
Platelet activation, signaling and aggregationREACTOMER-HSA-76002
GPVI-mediated activation cascadeREACTOMER-HSA-114604
Signal TransductionREACTOMER-HSA-162582
Signaling by EGFRREACTOMER-HSA-177929
GAB1 signalosomeREACTOMER-HSA-180292
Signaling by Insulin receptorREACTOMER-HSA-74752
Insulin receptor signalling cascadeREACTOMER-HSA-74751
IRS-mediated signallingREACTOMER-HSA-112399
PI3K CascadeREACTOMER-HSA-109704
Activation of AKT2REACTOMER-HSA-165158
PKB-mediated eventsREACTOMER-HSA-109703
PDE3B signallingREACTOMER-HSA-165160
mTOR signallingREACTOMER-HSA-165159
Inhibition of TSC complex formation by PKBREACTOMER-HSA-165181
Signalling by NGFREACTOMER-HSA-166520
NGF signalling via TRKA from the plasma membraneREACTOMER-HSA-187037
PI3K/AKT activationREACTOMER-HSA-198203
Signaling by PDGFREACTOMER-HSA-186797
Downstream signal transductionREACTOMER-HSA-186763
Signaling by VEGFREACTOMER-HSA-194138
VEGFA-VEGFR2 PathwayREACTOMER-HSA-4420097
VEGFR2 mediated vascular permeabilityREACTOMER-HSA-5218920
Signaling by SCF-KITREACTOMER-HSA-1433557
Signaling by ERBB2REACTOMER-HSA-1227986
Downregulation of ERBB2:ERBB3 signalingREACTOMER-HSA-1358803
Signaling by GPCRREACTOMER-HSA-372790
GPCR downstream signalingREACTOMER-HSA-388396
G-protein beta:gamma signallingREACTOMER-HSA-397795
G beta:gamma signalling through PI3KgammaREACTOMER-HSA-392451
Signaling by WntREACTOMER-HSA-195721
TCF dependent signaling in response to WNTREACTOMER-HSA-201681
Deactivation of the beta-catenin transactivating complexREACTOMER-HSA-3769402
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
Transcriptional Regulation by TP53REACTOMER-HSA-3700989
TP53 Regulates Metabolic GenesREACTOMER-HSA-5628897
Cell CycleREACTOMER-HSA-1640170
Cell Cycle, MitoticREACTOMER-HSA-69278
Mitotic G1-G1/S phasesREACTOMER-HSA-453279
G1/S TransitionREACTOMER-HSA-69206
Cyclin E associated events during G1/S transitionREACTOMER-HSA-69202
Vesicle-mediated transportREACTOMER-HSA-5653656
Membrane TraffickingREACTOMER-HSA-199991
Translocation of GLUT4 to the plasma membraneREACTOMER-HSA-1445148
Programmed Cell DeathREACTOMER-HSA-5357801
ApoptosisREACTOMER-HSA-109581
Intrinsic Pathway for ApoptosisREACTOMER-HSA-109606
Activation of BH3-only proteinsREACTOMER-HSA-114452
Activation of BAD and translocation to mitochondriaREACTOMER-HSA-111447
Developmental BiologyREACTOMER-HSA-1266738
Regulation of beta-cell developmentREACTOMER-HSA-186712
Regulation of gene expression in beta cellsREACTOMER-HSA-210745
AKT-mediated inactivation of FOXO1AREACTOMER-HSA-211163
Insulin resistanceKEGGhsa04931
Phospholipase D signaling pathwayKEGGko04072
Phospholipase D signaling pathwayKEGGhsa04072
AGE-RAGE signaling pathway in diabetic complicationsKEGGko04933
AGE-RAGE signaling pathway in diabetic complicationsKEGGhsa04933
Longevity regulating pathwayKEGGhsa04211
Longevity regulating pathway - multiple speciesKEGGko04213
Longevity regulating pathway - multiple speciesKEGGhsa04213
Regulation of TP53 ActivityREACTOMER-HSA-5633007
Regulation of TP53 Expression and DegradationREACTOMER-HSA-6806003
Regulation of TP53 DegradationREACTOMER-HSA-6804757
Regulation of TP53 Activity through Association with Co-factorsREACTOMER-HSA-6804759
Regulation of TP53 Activity through AcetylationREACTOMER-HSA-6804758
EGFR tyrosine kinase inhibitor resistanceKEGGko01521
Platinum drug resistanceKEGGko01524
Endocrine resistanceKEGGko01522
Platinum drug resistanceKEGGhsa01524
EGFR tyrosine kinase inhibitor resistanceKEGGhsa01521
Endocrine resistanceKEGGhsa01522
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224
Downregulation of ERBB2 signalingREACTOMER-HSA-8863795
RAB GEFs exchange GTP for GDP on RABsREACTOMER-HSA-8876198
Fluid shear stress and atherosclerosisKEGGko05418
Fluid shear stress and atherosclerosisKEGGhsa05418
Apelin signaling pathwayKEGGhsa04371

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA248NFKB1GenePathwayassociated
PA254NOS3GenePathwayassociated20124951
PA27749ELK1GenePathwayassociated
PA28212FOSGenePathwayassociated
PA296RELAGenePathwayassociated
PA30006JUNGenePathwayassociated
PA31353MYCGenePathwayassociated
PA31600NFKB2GenePathwayassociated
PA33304PIK3C2AGenePathwayassociated20124951
PA33305PIK3C2BGenePathwayassociated20124951
PA337STAT3GenePathwayassociated
PA338STAT5AGenePathwayassociated
PA36042SP1GenePathwayassociated
PA36183STAT1GenePathwayassociated
PA36184STAT2GenePathwayassociated
PA36185STAT4GenePathwayassociated
PA36186STAT5BGenePathwayassociated

References

Pubmed IDYearTitleCitations
163651682005Distinct roles of Akt1 and Akt2 in regulating cell migration and epithelial-mesenchymal transition.240
173323252007Twist transcriptionally up-regulates AKT2 in breast cancer cells leading to increased migration, invasion, and resistance to paclitaxel.206
151663802004A family with severe insulin resistance and diabetes due to a mutation in AKT2.148
125177982003Overexpression of AKT2/protein kinase Bbeta leads to up-regulation of beta1 integrins, increased invasion, and metastasis of human breast and ovarian cancer cells.139
198258272009MicroRNAs differentially regulated by Akt isoforms control EMT and stem cell renewal in cancer cells.111
191100522009Function of Akt/PKB signaling to cell motility, invasion and the tumor stroma in cancer.94
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
151026932004Prognostic significance of activated Akt expression in pancreatic ductal adenocarcinoma.78
190752302008Akt2 overexpression plays a critical role in the establishment of colorectal cancer metastasis.77
240567702013AKT2 is essential to maintain podocyte viability and function during chronic kidney disease.72

Citation

Deborah A. Altomare ; Joseph R. Testa

AKT2 (v-akt murine thymoma viral oncogene homolog 2)

Atlas Genet Cytogenet Oncol Haematol. 2007-07-01

Online version: http://atlasgeneticsoncology.org/gene/517/akt2