Akt2
- Known as:
- Akt2
- Catalog number:
- 000035A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- Akt2
Related genes to: Akt2
- Gene:
- AKT2 NIH gene
- Name:
- AKT serine/threonine kinase 2
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 19q13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1992-11-05
- Date modifiied:
- 2016-10-05
Related products to: Akt2
Related articles to: Akt2
- Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by hepatic steatosis, inflammation, fibrosis, and metabolic dysfunction, with limited therapeutic options currently available. This study investigated whether pharmacological inhibition of Galectin-3 (Gal-3), a β-galactoside-binding lectin implicated in inflammation and fibrosis, using modified citrus pectin (MCP), attenuates established MASH in ApoE-deficient mice. Mice were assigned to four groups: standard chow (CTL), standard chow plus MCP (CTL + MCP), Western diet with fructose-enriched drinking water (WD), and WD plus MCP (WD + MCP). MCP (1% in drinking water) was administered during the final four weeks of the 11-week experimental protocol, after the establishment of metabolic dysfunction and hepatic steatosis. Compared with untreated WD mice, WD + MCP mice exhibited improved glucose tolerance, as evidenced by a 22.9% reduction in glucose area under the curve ( = 0.01), and enhanced hepatic insulin signaling, reflected by a 254.1% increase in insulin-stimulated AKT2 phosphorylation ( = 0.0002). MCP treatment also reduced hepatic lipid accumulation (39.8%, = 0.0055) and hepatic triglyceride content (26.1%, = 0.0003), accompanied by reductions in circulating triglyceride and cholesterol concentrations. Furthermore, WD + MCP mice exhibited reduced hepatic Gal-3 expression (25.8%, = 0.0199), decreased F4/80 immunoreactivity (49.2%, = 0.0061), attenuated JNK phosphorylation (46.6%, = 0.0118), reduced collagen deposition (47.0%, = 0.0002), and lower plasma ALT (52.9%, = 0.0009) and AST (48.8%, = 0.04) activities. Collectively, these findings demonstrate that MCP attenuates multiple metabolic, inflammatory, fibrotic, and hepatic injury features of established Western diet-induced MASH, supporting Gal-3 as a promising therapeutic target and MCP as a potential pharmacological strategy for MASH. - Source: PubMed
Publication date: 2026/08/27
Santos Anne R MCruz Alessandra GCamargo Felipe NSantos Jessica D MModel Jorge F ASilva José F TMatos Sandro LAraujo Layanne C CCamporez João Paulo - (), a primary exacerbating factor in eczema, remains a prevalent pathogenic public-health threat. The mechanism of mast cell/basophil degranulation in the context of -exacerbated eczema remains unclear. We sought to investigate the direct effect of mast cell/basophil activation by isolated from patients with severe eczema undergoing topical steroid withdrawal (TSW) and understand the mechanism of berberine (BBR) in inhibiting this activation. Clinical strains (N = 8) were isolated from skin swabs of severe eczema patients and confirmed by sequencing. Human basophils (KU812), rat basophils (RBL-2H3) and murine mast cells (MC/9) were pre-treated with BBR for 48 h. and stimulated with heat-killed standard - and clinical strains for 45 min, and degranulation was measured. BBR's molecular-targets on basophils were identified by computational modeling and validated by qRT-PCR. BBR prevented degranulation following standard stimulation in KU812, RBL-2H3 and MC/9 cells. BBR dose-dependently inhibited degranulation in KU812. BBR inhibited TNF-α and IL-4 release, and markedly suppressed the expression of FcεR1 (α, β, γ), TNFα, MAPK1, MAPK3, AKT2, CASP9, and CCND1 following standard stimulation. BBR dose-dependently inhibited KU812 cell degranulation, markedly reduced TNF-α, IL-4, and MAPK1 and enhanced NFκB1A expression following clinical strain stimulation. BBR inhibition of -induced KU812 activation was at least associated with inhibition of MAPK-associated gene expression. This study provides novel insights into BBR's effect in preventing and human basophil interaction. - Source: PubMed
Publication date: 2026/09/03
Maskey Anish RKopulos DanielSpears MadisonWang Zhen-ZhenMo XianMusa IbrahimYang NanNowak-Wegrzyn AnnaChung DannaMaitland Anne LWang JulieTiwari Raj KSampson Hugh AGeliebter JanLi Xiu-Min - Obesity and type 2 diabetes mellitus (T2DM) are associated with chronic low-grade inflammation that sustains insulin resistance and metabolic dysfunction. Adipose tissue, through the secretion of adipokines and cytokines, plays a central role in shaping macrophage polarization and maintenance of an inflammatory microenvironment. While kinase-mediated signaling such as PI3K-AKT has been extensively studied, the contribution of phosphatases, particularly protein phosphatase 2A (PP2A), to macrophage polarization remains poorly defined. In this study, RAW264.7 macrophages exposed to inflammatory adipocyte-conditioned medium exhibited altered AKT isoform expression, including upregulation of AKT2 and downregulation of AKT1, along with activation of the PI3K, mTORC1/S6K pathway and suppression of protein phosphatase 2A (PP2A) activity, collectively promoting M1 pro-inflammatory polarization. To further elucidate the molecular mechanism, we performed molecular docking and 100 ns molecular dynamics simulations of both unphosphorylated AKT and ATP-bound (phosphorylated) AKT interacting with PP2A. The simulations revealed that phosphorylated AKT has higher binding affinity and greater structural stability with PP2A, facilitated by persistent hydrogen bonds with the regulatory and scaffolding subunits, suggesting a natural self-limiting mechanism that maintains the phosphorylation-dephosphorylation balance. We hypothesise that the experimentally observed reduction in PP2A levels in macrophages exposed to inflammatory adipocyte signals may impair this regulatory loop, favouring sustained pro-inflammatory signaling. These integrated experimental and computational findings highlight PP2A as a critical negative regulator of AKT-driven macrophage activation and suggest that therapeutic strategies aimed at restoring PP2A activity could prevent chronic inflammation in obesity and T2DM and could serve as a potential molecular target for mitigating metabolic inflammation. - Source: PubMed
Publication date: 2026/09/09
K Vinoth KannanT KothaiB S Lakshmi - Non-small-cell lung cancer (NSCLC), the predominant histological subtype accounting for more than 85% of lung cancer cases, remains the leading cause of cancer-related mortality worldwide. Despite the clinical advances afforded by targeted therapies, the frequent emergence of oncogenic driver mutations drives drug resistance and therapeutic failure, underscoring the critical need for novel molecular targets and alternative therapeutic strategies. AKT1, a serine/threonine kinase and central effector of the PI3K/AKT/mTOR signaling cascade, regulates key oncogenic processes including cell growth, survival, proliferation, and apoptotic evasion, and dysregulated hyperactivation is observed in 30-75% of NSCLC cases. Selective allosteric inhibition of AKT1, which targets the unique PH-kinase domain interface rather than the highly conserved ATP-binding pocket, has emerged as a more isoform-specific and therapeutically advantageous strategy compared with pan-AKT or ATP-competitive inhibition. In the present study, a ChemDiv AKT1-targeted compound library comprising 14,043 small molecules was subjected to hierarchical structure-based virtual screening using sequential high-throughput virtual screening (HTVS), standard precision (SP), and extra precision (XP) docking protocols, followed by binding free energy calculations using the MM-GBSA method. The top XP-ranked compounds, compound 1 (docking score: -11.771 kcal/mol), compound 2 (-11.428 kcal/mol), and compound 3 (-11.167 kcal/mol), achieved more favourable XP docking scores at the AKT1 allosteric site (PDB ID: 3O96) than established pan-AKT inhibitors, including MK-2206, miransertib, Bay1125976, and vevorisertib, although MM-GBSA rescoring did not reproduce this ordering. Comparative docking against the allosteric sites of AKT2 and AKT3 revealed a consistent preference for AKT1 across all three compounds, with a magnitude closely comparable to that of the reference allosteric ligand Inhibitor VIII, whose experimentally determined isoform rank order the protocol reproduced. Comprehensive 300-ns all-atom molecular dynamics (MD) analysis, encompassing RMSD and RMSF profiling, principal component analysis, dynamic cross-correlation matrix analysis, free energy landscape evaluation, and protein-ligand contact profiling, consistently demonstrated that compounds 1 and 2 maintain stable, high-affinity interactions with AKT1, exhibiting persistent engagement with the critical allosteric residues Trp80 and Tyr272 throughout the simulation trajectory. Furthermore, both compounds exhibited favourable pharmacokinetic profiles with predicted human oral absorption values over 80%, supporting their potential for preclinical development. - Source: PubMed
Publication date: 2026/09/08
Das RajuSultana ArminDas KantuChowdhury DipannitaChoi Seong WooWoo Joohan - Macrophage immune dysregulation in sepsis contributes to secondary infections and poor outcomes. Immunosuppression, a key feature of this dysregulation, has been linked to the acquisition of cellular senescence-like features in cancer. However, the mechanistic connection between immune tolerance, a well-established cellular model of immunosuppression, and macrophage senescence remains poorly understood. Here, using an in vitro model of lipopolysaccharide (LPS)-induced tolerance, we found that immune-tolerant macrophages acquired a senescent phenotype. Unexpectedly, nicotinamide phosphoribosyltransferase (NAMPT) mRNA and protein levels were markedly upregulated in tolerant macrophages despite profound suppression of MYC proto-oncogene (MYC), a canonical transcriptional regulator of NAMPT. Mechanistically, this paradoxical accumulation of NAMPT was driven by reduced expression of the RNA helicase DEAD-box helicase 6 (DDX6), thereby enhancing NAMPT mRNA stability. However, increased NAMPT abundance was uncoupled from its enzymatic activity owing to diminished AKT serine/threonine kinase 2 (AKT2)-mediated phosphorylation. Treatment with SC79, a pan-AKT activator, restored NAMPT phosphorylation and activity, attenuated senescence-associated markers, and enhanced bactericidal function in tolerant macrophages. In a murine model of sepsis, alveolar macrophages similarly exhibited reduced DDX6 and AKT2 expression, together with elevated NAMPT abundance, corroborating the in vitro findings. Collectively, these results identify a dual-layer regulatory mechanism in which DDX6 controls NAMPT abundance, whereas AKT2 dictates its activity. The uncoupling of NAMPT abundance from its enzymatic activity drives senescence during immune tolerance, identifying AKT2-NAMPT as a potential therapeutic axis to restore immune competence in sepsis. - Source: PubMed
Publication date: 2026/09/10
Li QilanHe MeiShi PeichiLi XuefengXu ZiliYao LuDu XinyiSong ChaoyingLi ChangJiang LangYang XiaoboZhang DingyuXu JiqianShang You