Ask about this productRelated genes to: SPHK2 antibody
- Gene:
- SPHK2 NIH gene
- Name:
- sphingosine kinase 2
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 19q13.33
- Locus Type:
- gene with protein product
- Date approved:
- 2002-07-05
- Date modifiied:
- 2018-03-13
Related products to: SPHK2 antibody
Related articles to: SPHK2 antibody
- Plant cells exhibit high plasticity for proliferation and differentiation, and pre-mRNA splicing makes an important contribution to this plasticity. Here, we show that the gene responsible for root redifferentiation defective4-1 (rrd4-1), a temperature-sensitive Arabidopsis thaliana mutant with defects in adventitious rooting and callus formation from hypocotyls, encodes a homolog of yeast Ntr1, which is involved in pre-mRNA splicing. Defective callus formation in rrd4-1 at the restrictive temperature of 28°C depended on the presence of kinetin (a synthetic cytokinin) in the callus-inducing medium. RNA-seq analysis revealed that genes involved in secondary cell wall biogenesis were upregulated, whereas those involved in cell cycle progression were downregulated, in a cytokinin-dependent manner in rrd4-1 at 28°C. Moreover, kinetin and the rrd4-1 mutation had broad effects on alternative splicing, particularly on lipid metabolism genes such as PTPLA, SPHK2, and ATNCER1. Consistent with this result, levels of very-long-chain fatty acid (VLCFA)-type sphingolipids were reduced in rrd4-1, and kinetin affected their contents during callus induction. Kinetin enhanced the inhibitory effect of the lipid synthesis inhibitor cerulenin on callus formation, and rrd4-1 was hypersensitive to cerulenin. Together, our data suggest that pre-mRNA splicing regulates cytokinin-mediated cellular dedifferentiation through the regulation of lipid metabolism gene splicing. - Source: PubMed
Publication date: 2026/05/06
Takeuchi AmiIshikawa ToshikiArae ToshihiroTogami JunichiNagamiya KenjiKoizumi KojiIkeda TakuyukiNagawa ShingoOhbayashi IwaiSugiyama MunetakaOhtani Misato - Our previous clinical studies show that all-trans retinoic acid (ATRA) induces a sustained response in patients with immune thrombocytopenia (ITP). However, its mechanisms of action remain unclear. In this study, we observed disorganized cytoskeleton and impaired proplatelet formation (PPF) in megakaryocytes from patients with ITP. Metabolite profiling revealed reduced sphingosine 1-phosphate (S1P) levels in ITP. Decreased sphingosine kinase 2 (SPHK2) expression was responsible for the low S1P levels in ITP. In addition, S1P was essential for activating S1P receptor 1 and Rac1, which regulate cytoskeletal reorganization and PPF. Furthermore, hypoxia-inducible factor-1α (HIF-1α) was shown to mediate SPHK2 and S1P production. Decreased HIF-1α expression in megakaryocytes from patients with ITP contributed to impaired PPF. We subsequently found that ATRA up-regulated HIF-1α and corrected impaired PPF in vitro and in vivo. These findings reveal that ATRA targets the HIF-1α/SPHK2/S1P pathway to improve PPF dysfunction, offering mechanistic insights into its clinical efficacy in ITP. - Source: PubMed
Publication date: 2026/05/06
Huang Qiu-ShaXue JingLiu Feng-QiChen QiZhang GaochaoSun Xue-YanWang ChencongYang LipingHou YuLi YueyingWang QianfeiPeng JunHou MingZhao XiaosuKong YuanChang YingjunZhao XiangyuHuang Xiao-JunZhang Xiao-Hui - Although chemotherapy-induced bone loss is well-recognized during breast cancer treatment, the underlying mechanism remains to be further elucidated, especially in patients with obesity. In this study, the objective was to investigate the impact of genomic silencing and pharmacological inhibition of S1P synthesis on bone loss in doxorubicin-induced obese breast cancer mice. In vitro study, upon the treatment of doxorubicin combined with palmitic acid, the S1P generated by 4T1 cells was significantly increased, resulting in an increase in osteoclastogenesis by activating the S1PR1/p-STAT3/NFATc-1 pathway in bone marrow-derived macrophages. In vivo study, pharmacological intervention with Sphingosine kinases (SPHK) antagonist SKI II or biological inhibition with SPHK1 and SPHK2 short hairpin RNA significantly reduced S1P production and rescued the obese breast cancer-bearing mice from doxorubicin-induced bone loss, manifested by the decreased osteoclastogenesis and recovered bone microarchitecture. Similarly, the administration of the S1PR1 antagonist FTY720 also alleviated bone loss in the breast cancer-bearing mice fed a high-fat diet. These studies indicate that genetic silencing and pharmacological inhibition can suppress S1P-dependent bone loss in doxorubicin-induced obese breast cancer mice. S1P shows promise as a potential drug target for preventing chemotherapy-induced bone loss in patients. - Source: PubMed
Publication date: 2026/03/30
Zhang YuShen HaoNiu JunjieHuang YingkangZhu CanWang YiChen YidaCheng XinyiYang HuilinZhang XianrongChen HaoZhang HongboShi Qin - MS is a lifelong autoimmune disorder striking the central nervous system (CNS). Despite the currently used disease-modifying therapies, patients are exposed to persistent neuropathy, pinpointing the need for supportive therapy. Neurotropic vitamins B1, B6 and B12 have been used to offer relief from immunological and neurological MS manifestations. This study aimed to provide some mechanistic insights into the relationship of B1/B6/B12 vitamin supplementation with the development of MS regarding lipid metabolism and epigenetics. In this cross-sectional observational study, blood samples were obtained from 53 MS patients, including 25 patients who had received daily vitamin B1/B6/B12 supplementation for over six months and 28 patients without supplementation. Plasma sphingosine-1-phosphate (S1P) and S1P receptor-1 (S1PR1) levels, lipid profile, and gene expression of ApoA1, sphingosine kinases 1&2 (SPHK1&2), S1PR1, as well as the lnc RNAs APOA1-AS and LISPR1 were evaluated. Gene ontology and KEGG pathway enrichment analyses were conducted. Vitamin B1/B6/B12 supplementation was associated with a more favorable lipid profile. Supplemented patients also exhibited higher ApoA1 and lower APOA1-AS expression compared with non-supplemented patients. Additionally, vitamin B1/B6/B12 supplementation was associated with lower expression levels of SPHK1, SPHK2, LISPR1, and S1PR1, and reduced circulating S1P concentrations. These findings imply significant associations between long-term vitamin B1/B6/B12 supplementation, alterations in lipid-related markers and sphingosine-associated signaling in MS patients. However, the observational design, selection bias and small sample size limit causal inference and may not fully capture the heterogeneity of MS population. Besides, supplement adherence was self-reported and not objectively verified, and circulating vitamin levels were not measured. - Source: PubMed
Publication date: 2026/05/01
Mehana Noha AGhaiad Heba RNooh Mohammed MAmer Mai AEl-Ghoneimy Lobna TalaatSafwat Maheera H - Sphingosine-1-phosphate (S1P) is a critical bioactive lipid mediator that regulates essential cellular processes-including proliferation, survival, migration, and inflammation-through binding to its cognate receptors (S1PRs) on the cell membrane or via direct intracellular actions. Sphingosine Kinase 2 (SphK2) has thus emerged as a promising therapeutic target. In this study, we designed and synthesized a novel series of SphK2 inhibitors (Q-series) based on the lead compound K145. Among these, compounds Q20 (IC = 2.6 ± 0.46 μM), Q24 (IC = 4.27 ± 1.51 μM), and Q25 (IC = 6.25 ± 0.62 μM) displayed potent and selective inhibition of SphK2, while showing negligible activity against SphK1 (IC > 50 μM). Notably, Q25 exhibited significant anti-proliferative effects against multiple colorectal cancer cell lines (LOVO, SW480, SW620, HT-29), with IC values of 8.09 ± 4.36, 7.77 ± 2.48, 7.38 ± 3.41, and 6.41 ± 2.46 μM, respectively. Mechanistically, Q25 induced S-phase cell cycle arrest and apoptosis. The Q-series compounds (Q20, Q24, Q25) also demonstrated favorable metabolic stability in human liver microsomes, characterized by prolonged half-lives (T > 90 min), low intrinsic clearance (CLint(mic) < 15 μL/min/mg), and high parent compound recovery (∼50% remaining after incubation). In vivo pharmacokinetic studies in mice indicated that Q25 is rapidly metabolized, classified as a high-clearance compound, and undergoes extrahepatic elimination. In a SW480 xenograft mouse model, Q25 effectively inhibited tumor growth without observable toxicity. Western blot analysis suggested that its anti-tumor effect is associated with reduced S1P production and subsequent suppression of the NF-κB pathway. In summary, these findings identify Q25 as a promising, selective SphK2 inhibitor worthy of further development as an anticancer agent. - Source: PubMed
Publication date: 2026/04/26
Liu JunruShi XiujuanYang XinmeiZhao XiaodongHuang FuxunLi ZhaoyangLiu YuanyuanGao YuqiFeng JingtongQu ZhiqiangYi ChenghuaYang YeLiang ZihanYao QingqiangLiu Bo