AKT1 (phospho-Ser473) Antibody
- Known as:
- AKT1 (phosphorilated-Ser473) Antibody
- Catalog number:
- abx000166
- Product Quantity:
- EUR
- Category:
- -
- Supplier:
- Abbexa
- Gene target:
- AKT1 (phospho-Ser473) Antibody
Related genes to: AKT1 (phospho-Ser473) Antibody
- Gene:
- AKT1 NIH gene
- Name:
- AKT serine/threonine kinase 1
- Previous symbol:
- -
- Synonyms:
- RAC, PKB, PRKBA, AKT
- Chromosome:
- 14q32.33
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2019-04-23
Related products to: AKT1 (phospho-Ser473) Antibody
Related articles to: AKT1 (phospho-Ser473) Antibody
- Neural progenitor cell (NPC) proliferation is fundamental for population expansion and brain development. G phase control determines the cell cycle duration of NPCs and thereby affects their proliferation efficiency. However, the molecular mechanisms governing G phase progression in NPCs remain unclear. Here, we show that AKT gain-of-function mutations and pharmacological inhibition exert opposing effects on NPC proliferation. Consistently, Emx1-Cre-mediated deletion of Akt1/2/3 in mice impairs NPC proliferation and disrupts cortical development. We find that AKT deficiency induces G phase arrest and prolongs the cell cycle of NPCs. Mechanistically, we demonstrate that AKT-mediated phosphorylation inhibits the activity of CRL4 E3 ubiquitin ligase to safeguard cyclin D2 (CCND2) stability. Specifically, AKT phosphorylates DDB1, the adaptor of CRL4, which disrupts its interaction with CCND2 and reduces its degradation. These findings reveal a post-translational mechanism impacting NPC cell cycle and cortical morphogenesis, providing insight into the etiology of malformations of cortical development. - Source: PubMed
Publication date: 2026/04/27
Wang HeLiu PanmiaoWang RunminGu HanwenZhu TingtingChen GuiquanYang Jian-Jun - Most patients with advanced/metastatic hormone receptor-positive, HER2-negative breast cancer receive first-line therapy with cycline-dependent kinase 4/6 inhibitors plus endocrine therapy. Almost universally, these patients eventually progress due to the emergence of resistant cancer clones. Targeting the PIK3CA/AKT1/PTEN pathway is a way of overcoming resistance. Recently, the oral, selective AKT kinase inhibitor capivasertib has been approved for the treatment of estrogen receptor-positive/human HER2-growth factor receptor-2 advanced BC with alterations in PIK3CA/AKT1/PTEN, in combination with fulvestrant after progression on endocrine therapy. We performed a narrative review to recapitulate the available evidence about capivasertib in the management of advanced hormone receptor-positive, HER2-negative breast cancer, focusing on studies that address preclinical rationale, pharmacology, and clinically relevant problems. - Source: PubMed
Publication date: 2026/03/31
Valerio Maria RosariaSambataro DanielaMartorana FedericaGreco MartinaMesi ChiaraGebbia VittorioVigneri PaoloScandurra Giuseppa - HIV and cocaine are known to disrupt neuronal signaling and contribute to neurocognitive dysfunction, yet the underlying molecular mechanisms are not clear. In this study, we delineate the underlying molecular mechanism by which HIV and/or cocaine enhance Tau phosphorylation (p-Tau S396), a marker of Tau-mediated neuropathies. Furthermore, we elucidate how these two independent neuropathogenic factors, cocaine and HIV, exploit distinct yet convergent signaling pathways to drive this pathological event. We demonstrate that HIV robustly activates and upregulates RSK1, which functions upstream of AKT and promotes Tau phosphorylation through an AKT-independent mechanism while simultaneously inactivating GSK3β via serine-9 phosphorylation (p-GSK3β S9). However, cocaine not only activates RSK1 but also strongly stimulates AKT1, resulting in sustained GSK3β inhibition and persistent Tau phosphorylation. Notably, Tau phosphorylation persists even under conditions of GSK3β inactivation in both HIV and cocaine exposure, revealing a previously unrecognized GSK3β-independent mechanism of Tau modification. Collectively, these findings identify RSK1 as the primary mediator of Tau phosphorylation upon HIV and/or cocaine exposure, and uncover a novel RSK1-driven, GSK3β-independent pathway contributing to Tauopathy. Through a combination of immunofluorescence, immunoblotting, genetic knockout, and overexpression approaches, we establish RSK1 as a central signaling hub linking the AKT-GSK3β pathway to Tau phosphorylation. We demonstrate that RSK1 operates as a critical upstream regulator of AKT and GSK3β signaling, playing dual roles, both activating AKT and suppressing GSK3β, thereby uncovering a novel layer of pathways that regulates Tau phosphorylation. The reproducibility of these main signaling pathways across SH-SY5Y neurons, mixed cell 3D spheroids, and human brain organoids underscores the robustness and biological relevance of this mechanism. Collectively, these findings reveal mechanistic convergence of HIV and cocaine on RSK1-dependent signaling and provide critical insight into how diverse neuropathic / neuropathological factors remodel neuronal signaling to drive Tau-associated dysfunction. These findings provide novel mechanistic insight into the molecular underpinnings of neuro-HIV and substance abuse associated Tauopathy. By identifying RSK1 as a master regulator and demonstrating that Tau phosphorylation can bypass GSK3β inhibition, our study advances understanding of signaling complexity and highlights new opportunities for therapeutic intervention. Targeting RSK1 may represent a promising strategy to mitigate Tau pathology, induced due to insoluble aggregates of phosphorylated Tau, a common factor promoting cognitive decline not only in individuals with Alzheimer's disease but also in those exposed to cocaine or/and infected with HIV. - Source: PubMed
Publication date: 2026/04/16
Sharma Adhikarimayum LakhikumarSariyer Ilker KNaik Ulhas PTyagi Mudit - - Source: PubMed
Publication date: 2026/04/26
Chanda Hemantha Mani Kumar ChakravarthiKatari Sudheer Kumar - In drug discovery tasks, achieving a balance between high biological activity toward therapeutic targets and synthetic chemical feasibility is critically important. While the recently proposed deep learning-based molecular generation models have enabled explorations of vast chemical spaces, most existing approaches do not consider synthetic routes for generated compounds. To address this issue, TRACE-GFN is proposed for molecular optimization; this method incorporates chemical reaction pathways into a quantitative structure-activity relationship (QSAR)-guided molecular design procedure. The method integrates a transformer model to explicitly learn chemical reactions with a generative flow network (GFlowNet) that efficiently samples diverse candidates. In benchmark experiments involving dopamine receptor D2 (DRD2), AKT serine/threonine kinase 1 (AKT1), and C-X-C motif chemokine receptor 4 (CXCR4), TRACE-GFN demonstrated the ability to identify compounds with high QSAR values while maintaining strong diversity, outperforming the existing molecular generation models. These results demonstrate that the proposed model can efficiently explore promising compounds while accounting for real-world chemical reactions. The source code is publicly available under an MIT license at https://github.com/sekijima-lab/TRACE-GFN. - Source: PubMed
Publication date: 2026/04/25
Nakamura ShogoYasuo NobuakiSekijima Masakazu