Ask about this productRelated genes to: IP6K2 antibody
- Gene:
- IP6K2 NIH gene
- Name:
- inositol hexakisphosphate kinase 2
- Previous symbol:
- IHPK2
- Synonyms:
- -
- Chromosome:
- 3p21.31
- Locus Type:
- gene with protein product
- Date approved:
- 2002-01-04
- Date modifiied:
- 2014-11-18
Related products to: IP6K2 antibody
Related articles to: IP6K2 antibody
- Phosphate-induced vascular calcification in chronic kidney disease is linked to cardiovascular mortality. This calcification process involves vascular smooth muscle cells (VSMCs), which can promote a pro-calcific environment in the vascular wall. However, the mechanisms underlying a putative phosphate sensing of VSMCs to modulate pro-calcific signaling are insufficiently clarified. In mammals, three isoforms of the inositol hexakisphosphate kinase (IP6K) exist, which have been implicated in cellular phosphate homeostasis. Therefore, each IP6K isoform was silenced in calcifying primary human aortic VSMCs. and mRNA expression were increased in calcifying VSMCs. Silencing of either IP6K1 or IP6K2 ameliorated phosphate-induced pro-calcific markers expression and VSMC calcification. mRNA expression was not modified during calcifying conditions, but IP6K3 silencing still resulted in some anti-calcific effects. Mechanistically, the IP6K product 5-IP7 may act as a potent inhibitor of AKT kinase signaling. Accordingly, pro-calcific conditions induced only transient AKT phosphorylation, and IP6K2 silencing increased AKT phosphorylation in calcifying VSMCs. In turn, AKT inhibition blunted the protective effects of IP6K2 knockdown, while serum- and glucocorticoid-inducible kinase 1 (SGK1) inhibition restored these effects. These observations indicate a role for IP6Ks during phosphate-induced VSMC calcification, which could be mediated by an altered balance between AKT and SGK1 signaling. - Source: PubMed
Publication date: 2026/01/30
Bahiraii SheydaJannat IsratulPlösser SarahRazazian MehdiVoelkl JakobAlesutan Ioana - Dioxin-like pollutants, especially 2,3,7,8-Tetrachlorodibenzo-p-dioxin, are recognized human carcinogens. Retrospective studies suggest a link between dioxins and soft tissue sarcomas, including liposarcoma, but mechanisms remain unclear. This study explores the toxicological effects of dioxins on liposarcoma, identifies key proteins, and proposes potential solutions. We identified dioxin- and liposarcoma-related targets via databases, analyzed overlaps through enrichment and network toxicology, and validated them with phenotypic and clinical data. We built a prediction model using 117 combinations of machine learning algorithms, confirmed the results with molecular docking and simulations, and proposed therapies through drug experiments. TCDD modulates adipocytic malignancy through activation of xenobiotic response pathways, disruption of cellular metabolism, and interactions with cancer-related receptors. AhR partially mediates this toxicological effect, and five key proteins, including CDH3, ADORA2B, MMP14, IP6K2, and HTR2A, are used to predict the development of dioxin-related liposarcoma. The selective HTR2A receptor antagonist ketanserin has the potential to alleviate this toxicological impact. Our study presents an efficient, cost-effective toxicological analysis using network toxicology, offering new insights into dioxin-associated liposarcoma. - Source: PubMed
Publication date: 2025/11/17
Chenhe ZhangAobo ZhuangXiao ZhouHan GaoLongshang WangZhe XiYingxue ChengHuichen LiJincheng WuWei ZengWengang Li - Knockout mice have served as excellent model systems to investigate the functions of specific mammalian proteins at the organismal level. Several studies on tissue-specific or whole-body depletion of individual IP6 kinase (IP6K) paralogs have shed light on myriad roles for their product, the inositol pyrophosphate 5-InsP, in different physiological processes and pathological states. The loss of Ip6k1, Ip6k2, or Ip6k3 leads predominantly to nonoverlapping phenotypes in mice, reflecting their differential tissue, cell type, and subcellular distribution. Using the example of Ip6k1 knockout mice, and the stark phenotype of male infertility resulting from the depletion of condensed spermatids in the testes of these mice, this chapter provides detailed methods for the use of knockout mice as a model to study the functions of IP6Ks. We begin with protocols for the maintenance and breeding of the mouse colony, with instructions to genotype offspring from the mating of heterozygous mice carrying one Ip6k1 knockout allele. We then provide methods for the histopathological comparison of tissues in wild-type versus knockout mice by hematoxylin and eosin staining, and the detection of IP6K1 expression in specific tissues and subcellular compartments by western blotting and immunofluorescence. - Source: PubMed
Anindita ASen JayrajBhandari Rashna - E-cadherin downregulation is an epithelial-mesenchymal transition hallmark canonically attributed to transcriptional repression. Here we delineate a metabolite-driven endocytic route of E-cadherin downregulation in inflammation-associated colorectal cancer (CRC). Specifically, IP kinase-2 (IP6K2), a 5-diphosphoinositol pentakisphosphate (5-IP) synthase upregulated in patients with CRC, is activated via a ROS-Src phosphorylation axis elicited by dextran sulfate sodium (DSS), generating 5-IP around adherens junction (AJ) to promote E-cadherin endocytosis and the transcriptional activities of β-catenin. Mechanistically, 5-IP inhibits inositol 5-phosphatases such as OCRL to promote PI(4,5)P-mediated endocytic adaptor recruitment. Depleting 5-IP or overexpressing a 5-IP binding-deficient OCRL mutant confers resistance to DSS-elicited AJ disruption. Intestinal epithelium-specific IP6K2 deletion attenuates DSS-induced colitis/CRC, whereas an IP6K2 isoform-selective inhibitor protects wild-type but not IP6K2 mice against DSS insult. Thus, 5-IP is an oncometabolite whose stimulus-dependent synthesis relieves a PI(4,5)P dephosphorylation-based endocytic checkpoint, leading to AJ disassembly and protumorigenic β-catenin activation. Targeting IP6K2 could strengthen intestinal epithelial barrier against inflammation and cancer. - Source: PubMed
Publication date: 2025/08/26
Zhang HongyunZhang BoboZhao YueboSu YangPeng YifanYang XiaoliZhao HongmingLiu HongyuFeng JiePei HongjingZhang WenyongHuang NiuJiang KaiIto MasatoshiLiu GuizhenJork NicolasAnderson Karen EZhao LiNagata EiichiroJessen Henning JHawkins Philip TDu ChangzhengRao Feng - Parkinson’s disease (PD) is a highly heterogeneous disorder with distinct phenotypes that can develop well before motor symptoms appear. Recently, two main phenotypes based on the different pathological spreading patterns of PD have been proposed: “body-first”, where α-synuclein pathology begins in the peripheral nervous system and spreads symmetrically from bottom-up, and “brain-first”, where pathology starts in the brain and spreads asymmetrically downwards. However, no studies have assessed these phenotypes across both prodromal and clinical PD stages, tracked their pathological progression in vivo or identified potential underlying biological mechanisms. - Source: PubMed
Publication date: 2025/06/20
Passaretti MassimilianoVeréb DanielMijalkov MiteChang Yu-WeiZhao HangZufiria-Gerbolés BlancaSun JiaweiVolpe GiovanniRivera NataliaBologna MatteoPereira Joana B