Phospho-AKT2 (Ser474) Antibody
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Description
Biological Context of AKT2 and Ser474 Phosphorylation
AKT2 is one of three isoforms (AKT1, AKT2, AKT3) within the AKT kinase family. It regulates:
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Glucose metabolism: Mediates insulin-induced GLUT4 translocation to the cell membrane .
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Cell survival: Phosphorylates apoptosis-related proteins like BAD and FOXO transcription factors .
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Protein synthesis: Activates mTORC1 via TSC2 phosphorylation, promoting ribosome biogenesis .
Phosphorylation at Ser474:
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Occurs in the hydrophobic motif (HM) of AKT2’s C-terminal tail.
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Required for full kinase activation alongside Thr309 phosphorylation .
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Facilitates structural rearrangement, enhancing substrate binding and catalytic activity .
Role in Insulin Signaling
Studies in 3T3-L1 adipocytes reveal:
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Loss of Ser474 phosphorylation reduces AKT2 activity by ~50%, impairing insulin-stimulated processes:
Implications in Cancer
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Constitutively active AKT2 (phosphorylated at Ser474) is observed in cancer cell lines and tissues, driving proliferation and survival .
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Inhibitors targeting AKT’s hydrophobic motif (e.g., MK2206) show therapeutic potential but risk metabolic side effects like hyperglycemia .
Implications in Disease and Therapeutics
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Cancer: Overactivation of AKT2-Ser474 correlates with tumor progression and drug resistance .
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Metabolic Disorders: Impaired Ser474 phosphorylation disrupts glucose homeostasis, linking AKT2 dysfunction to diabetes .
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Therapeutic Targeting: Selective inhibition of AKT2-Ser474 phosphorylation could mitigate oncogenic signaling while preserving metabolic functions .
Key Applications in Research
Product Specs
Form
Supplied at 1.0mg/mL in phosphate buffered saline (without Mg2+ and Ca2+), pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol.
Lead Time
Typically, we are able to ship products within 1-3 business days of receiving your order. Delivery time may vary depending on the purchase method or location. Please consult your local distributors for specific delivery timeframes.
Synonyms
Akt2 antibody; AKT2_HUMAN antibody; HIHGHH antibody; Murine thymoma viral (v-akt) homolog 2 antibody; murine thymoma viral (v-akt) homolog-2 antibody; Oncogene AKT2 protein kinase B beta antibody; PKB antibody; PKB beta antibody; PKBB antibody; PKBBETA antibody; PRKBB antibody; Protein kinase Akt 2 antibody; Protein kinase Akt-2 antibody; Protein kinase B beta antibody; RAC beta antibody; rac protein kinase beta antibody; RAC-BETA antibody; RAC-beta serine/threonine-protein kinase antibody; RAC-PK-beta antibody; RACbeta antibody; v akt murine thymoma viral oncogene homolog 2 antibody; V-AKT murine thymoma viral oncogene homolog 2 antibody
Target Names
Uniprot No.
Target Background
Function
AKT2 is one of three closely related serine/threonine-protein kinases (AKT1, AKT2, and AKT3) collectively known as the AKT kinase. These kinases play a crucial role in regulating a wide range of cellular processes, including metabolism, proliferation, cell survival, growth, and angiogenesis. This regulation is primarily mediated through serine and/or threonine phosphorylation of various downstream substrates. Over 100 potential substrate candidates have been identified to date, but for the majority of them, isoform specificity remains undefined. AKT is responsible for regulating glucose uptake by facilitating insulin-induced translocation of the SLC2A4/GLUT4 glucose transporter to the cell surface. Phosphorylation of PTPN1 at 'Ser-50' negatively regulates its phosphatase activity, preventing dephosphorylation of the insulin receptor and the attenuation of insulin signaling. Phosphorylation of TBC1D4 triggers the binding of this effector to inhibitory 14-3-3 proteins, a crucial step in insulin-stimulated glucose transport. AKT also regulates glucose storage in the form of glycogen by phosphorylating GSK3A at 'Ser-21' and GSK3B at 'Ser-9', leading to inhibition of its kinase activity. Phosphorylation of GSK3 isoforms by AKT is also believed to be a mechanism driving cell proliferation. AKT further regulates cell survival by phosphorylating MAP3K5 (apoptosis signal-related kinase). Phosphorylation of 'Ser-83' reduces MAP3K5 kinase activity stimulated by oxidative stress, thus preventing apoptosis. AKT mediates insulin-stimulated protein synthesis by phosphorylating TSC2 at 'Ser-939' and 'Thr-1462', thereby activating mTORC1 signaling, ultimately leading to both phosphorylation of 4E-BP1 and activation of RPS6KB1. AKT is involved in the phosphorylation of members of the FOXO factors (Forkhead family of transcription factors), resulting in binding of 14-3-3 proteins and cytoplasmic localization. Specifically, FOXO1 is phosphorylated at 'Thr-24', 'Ser-256', and 'Ser-319'. FOXO3 and FOXO4 are phosphorylated at equivalent sites. AKT plays a significant role in regulating NF-kappa-B-dependent gene transcription and positively regulates the activity of CREB1 (cyclic AMP (cAMP)-response element binding protein). Phosphorylation of CREB1 induces the binding of accessory proteins necessary for the transcription of pro-survival genes such as BCL2 and MCL1. AKT phosphorylates 'Ser-454' on ATP citrate lyase (ACLY), potentially regulating ACLY activity and fatty acid synthesis. It activates the 3B isoform of cyclic nucleotide phosphodiesterase (PDE3B) via phosphorylation of 'Ser-273', resulting in reduced cyclic AMP levels and inhibition of lipolysis. AKT phosphorylates PIKFYVE on 'Ser-318', leading to increased PI(3)P-5 activity. The Rho GTPase-activating protein DLC1 is another substrate, and its phosphorylation is implicated in regulating cell proliferation and cell growth. AKT acts as a key modulator of the AKT-mTOR signaling pathway, controlling the tempo of newborn neuron integration during adult neurogenesis, including correct neuron positioning, dendritic development, and synapse formation. AKT signals downstream of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects of various growth factors, including platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin, and insulin-like growth factor I (IGF-I). AKT mediates the antiapoptotic effects of IGF-I. It is essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. AKT may be involved in regulating placental development. One of the few specific substrates of AKT2 recently identified is PITX2. Phosphorylation of PITX2 impairs its association with the CCND1 mRNA-stabilizing complex, thereby shortening the half-life of CCND1. AKT2 appears to be the principal isoform responsible for regulating glucose uptake. AKT2 phosphorylates C2CD5 on 'Ser-197' during insulin-stimulated adipocytes. AKT2 is also specifically involved in skeletal muscle differentiation, one of its substrates in this process being ANKRD2. Down-regulation by RNA interference reduces the expression of the phosphorylated form of BAD, resulting in the induction of caspase-dependent apoptosis. AKT2 phosphorylates CLK2 on 'Thr-343'.
Gene References Into Functions
- AKT2 inhibition serves as a potent therapeutic target against cancer stem cells. PMID: 29667444
- AKT2 and XIST expression have been identified as potential biomarkers involved in the effects of ATP5J in colorectal cancer. PMID: 29484395
- This study provides the first evidence that miR-608 acts as a tumor suppressor in A549 and SK-LU-1 cells through the regulation of AKT2. PMID: 29075783
- The current study suggests that PHB2 may promote prostate cancer cell migration by inhibiting the expression of AKT2. These findings contribute to understanding the role of PHB2 in prostate cancer migration and malignancy. PMID: 29207197
- Data reveal that S131 of Akt2 is not phosphorylated by CK2 despite the presence of the conserved consensus sequence recognized by CK2 (S/T-x-x-E/D/pS/pT). A single sequence element, a T at position n+1, hinders phosphorylation, leading to an alpha-helix structure that prevents recognition of its own consensus by CK2. Using synthetic peptides, the study suggests that Akt2 S131 could be phosphorylated by kinases of the Plk family. PMID: 29494643
- Findings demonstrate that DNA double-strand breaks (DSBs) trigger pro-survival autophagy in an ATM- and p53-dependent manner, which is curtailed by AKT2 signaling. PMID: 28837154
- Genetic association studies in a Finnish male population: Data suggest that a partial loss-of-function variant in AKT2 (p.Pro50Thr) is associated with type 2 diabetes in the studied population. This AKT2 variant is linked to reduced insulin-mediated glucose uptake in multiple insulin-sensitive tissues. PMID: 29141982
- The miR2965p/AKT2 axis plays crucial roles in hepatocellular carcinoma carcinogenesis and progression. PMID: 28586057
- miR296 is downregulated in tissue from patients with pancreatic cancer and pancreatic carcinoma cell lines. These findings suggest that it may function as a tumor suppressor by inhibiting the growth, migration, and invasion of pancreatic cancer cells. AKT2 was validated as a direct target of miR296 in pancreatic cancer cells. PMID: 28534950
- miR-143-3p acts as a novel tumor suppressive miRNA by regulating gastric tumor growth, migration, and invasion through directly targeting the AKT2 gene. PMID: 28404925
- Our findings suggest that Akt2 might be associated with resistance to anti-EGFR therapies, particularly the use of erlotinib against pancreatic cancer, and that this resistance can be overcome by combined treatment with a PI3K inhibitor. Akt2 expression could become a predictive biomarker for erlotinib resistance in pancreatic cancer. PMID: 28440469
- This study investigated the action of linoleic acid (LA) on cell migration and neoplasm invasiveness of breast cancer cells. Findings show Akt2 activation requires EGFR and PI3K activity, whereas migration and invasion depend on FFAR4, EGFR, and PI3K/Akt activity. PMID: 28456993
- Analysis of genomic data from The Cancer Genome Atlas (TCGA) demonstrated coamplification of CCNE1 and AKT2. Overexpression of Cyclin E1 and AKT isoforms, in addition to mutant TP53, imparted malignant characteristics in untransformed fallopian tube secretory cells, the dominant site of origin of high-grade serous ovarian cancer. PMID: 27663592
- Recent studies reveal that AKT2-NOX2 signaling plays critical roles in Ca mobilization, ROS generation, degranulation, and control of the ligand-binding function of cell surface molecules, thereby promoting heterotypic cell-cell interactions in thromboinflammation. PMID: 28650848
- The expression levels of AKT2 and CDC25C showed lower expression in neural tube defects. Additionally, the percentage of methylated region of the AKT2 promoter was increased in neural tube defects. PMID: 27871477
- This report examines the frequency of genetic variation in Akt2 and discusses its link to type 2 diabetes. PMID: 28931550
- IRF5 and IRF5 disease-risk variants increase glycolysis and human m1 macrophage polarization by regulating proximal signaling and Akt2 activation. PMID: 27545875
- The direct interaction of AKT2 and EF2 was found to be dynamically regulated in embryonic rat cardiomyocytes. PMID: 23823123
- This study identifies MTSS1 as a new Akt2-regulated gene and points to suppression of MTSS1 as a key step in the metastasis-promoting effects of Akt2 in CRC cells. PMID: 28068324
- Akt2, Erk2, and IKK1/2 phosphorylate Bcl3, converting Bcl3 into a transcriptional coregulator by facilitating its recruitment to DNA. PMID: 28689659
- Results indicate that AKT2 modulates pulmonary fibrosis through inducing TGF-beta1 and IL-13 production by macrophages. Inhibition of AKT2 may be a potential therapeutic strategy for treating idiopathic pulmonary fibrosis. PMID: 28455433
- The p.Glu17Lys mutation of AKT2 confers low-level constitutive activity upon the kinase and produces hypoglycemia with suppressed fatty acid release from adipose tissue, but not fatty liver, hypertriglyceridemia, or elevated hepatic de novo lipogenesis. PMID: 28541532
- Studies provide evidence that AKT2 counteracts oxidative-stress-induced apoptosis and is required for alpha-beta thymocyte survival and differentiation. It also plays a critical role in antagonizing cardiomyocyte apoptosis. [review] PMID: 26953242
- This study examines the role of Akt2 in human lung cancer cell proliferation, growth, motility, invasion, and endothelial cell tube formation. PMID: 26234648
- This study demonstrates novel regulatory circuits involving miR-148a-3p/ERBB3/AKT2/c-myc and DNMT1 that control bladder cancer progression, which may be useful in developing more effective therapies against bladder cancer. PMID: 27906180
- Both in the animal model and in human age-related macular degeneration (AMD), the AKT2-NF-kappaB-LCN-2 signaling axis is involved in activating the inflammatory response. PMID: 28026019
- This study identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and an increased risk of type 2 diabetes. PMID: 28341696
- AKT2 can regulate miR-200a in a histology- or stage-specific manner, and this regulation is independent of subsequent involvement of miR-200a in epithelial-mesenchymal transition. PMID: 27189341
- Quinoline-type inhibitors bind in the Akt2 PH domain. PMID: 28036396
- TGF-beta signaling through Akt2 induces phosphorylation of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) at serine-43 (p-hnRNP E1), driving epithelial to mesenchymal transition and metastasis. PMID: 27067543
- miR-29b plays an important role in TGF-beta1-mediated epithelial-mesenchymal transition in ARPE-19 cells by targeting Akt2. PMID: 25263462
- miR-148a functions as a tumor suppressor in renal cell carcinoma by targeting AKT2. PMID: 27878305
- MiR-650 could inhibit the proliferation, migration, and invasion of rheumatoid arthritis synovial fibroblasts through targeted regulation of AKT2 expression. PMID: 28129626
- High AKT2 expression is associated with gallbladder cancer. PMID: 26803515
- miR-302b inhibits SMMC-7721 cell invasion and metastasis by targeting AKT2. PMID: 26254095
- No association has been found between AKT2 polymorphisms and esophageal squamous cell carcinoma risk. PMID: 26828791
- High AKT2 expression is associated with ovarian cancer. PMID: 26512921
- Active, phosphorylated Akt2 translocates to the nucleus in Notch-expressing cells, resulting in GSK-3beta inactivation in this compartment. PMID: 26711268
- AKT2 controls endothelial Jagged1 expression and, thereby, Notch signaling, regulating VSMC maintenance. PMID: 26971877
- These studies identify Akt2 as a critical kinase that regulates radixin phosphorylation and leads to Mrp-2 translocation and function. PMID: 26500117
- miR-612 directly suppressed AKT2, which in turn inhibited the downstream epithelial-mesenchymal transition-related signaling pathway. PMID: 26158514
- The correlation between RLN2 and p-AKT or RLN2 and p-ERK1/2 expression was investigated. PMID: 26229955
- This study explores the biological effect of Akt2 in colorectal cancer cells. PMID: 25134663
- 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. PMID: 26102366
- miR-615-5p inhibits pancreatic cancer cell proliferation, migration, and invasion by targeting AKT2. PMID: 25856297
- QSAR-based docking studies identify marine algal callophycin A as an inhibitor of protein kinase B beta. PMID: 25936945
- This study assayed the expression of myosin II, which is a powerful predictor of the use of ZEB2/Akt2 as a marker for tumor progression in serous ovarian cancers. PMID: 25894377
- Up-regulation of AKT2 was associated with chemoresistance in renal cell carcinoma. PMID: 25951903
- Findings suggest that AKT2 may be one of the targets of miR29s in gastric cancer. PMID: 25428377
- PIK3CA and AKT2 mutations occurred at a low frequency in gastric cancer. PMID: 25771729
Database Links
Involvement In Disease
Diabetes mellitus, non-insulin-dependent (NIDDM); Hypoinsulinemic hypoglycemia with hemihypertrophy (HIHGHH)
Protein Families
Protein kinase superfamily, AGC Ser/Thr protein kinase family, RAC subfamily
Subcellular Location
Cytoplasm. Nucleus. Cell membrane; Peripheral membrane protein. Early endosome.
Tissue Specificity
Expressed in all cell types so far analyzed.
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