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Sk1 and Sk2 are not redundant in biological function and are essential for diverse physiological functions in Drosophila
Deletion of amino acids (182)VSGDGI(187) perturbed PA-AtSPHK1 binding, indicating an essential role of these six amino acids in PA-AtSPHK1 binding.
findings indicate a role of SPHK1 in modulating FB1-triggered cell death via SA and JA pathway interactions.
SPHK/phyto-S1P and PLDalpha1A are co-dependent in amplification of response to ABA, mediating stomatal closure in Arabidopsis.
Sphingosine kinase 1 phosphorylates sphingosine-1-phosphate and phytosphingosine-1-phosphate, and is coordinately regulated with sphingosine-1-phosphate phosphatase.
Melatonin administration significantly inhibited those changes and induced a decreased immunoreactivity for rabbit hemorrhagic disease virus VP60 antigen in the liver. Results obtained indicate that the SphK1/S1P system activates in parallel to viral replication and the inflammatory process induced by the virus.
High SPHK1 expression is significantly associated with aggressive colorectal cancer behavior and worse overall survival, and is an independent predictor of distant metastasis
Low SPHL1 expression is associated with Huntington's disease.
Study shows that both in prostate and breast cancers vascular endothelial growth factor and sphingosine-kinase-1 are independently regulated by mammalian target of rapamycin 1.
High SPHK1 expression is associated with pulmonary arterial hypertension.
TGF-beta1 appears to promote CAD through the induction of cell apoptosis by upregulating SPHK1 expression and further upregulating its downstream TIMP-1.
Through field template screening, we have identified a new SK1 inhibitor, SK-F, which demonstrated antitumour activity in vitro and in vivo without overt toxicity when combined with docetaxel
UCMSCs transfected by SPK1 gene potentially offer a novel mode for the treatment of MS.
Neuronal SphK1 acetylates COX2 and contributes to pathogenesis in Alzheimer's disease patients and in a transgenic mouse model.
siRNA-mediated knockdown of Sphk2 but not SphK1 resulted in a reduction of cargo content in purified exosomes
These findings suggested that miR125b may regulate Alzheimer's disease (AD), and neuronal cell growth and apoptosis, via the regulation of inflammatory factors and oxidative stress by SphK1; therefore, miR125b may be involved in the development of AD.
these findings suggest that SphK1 may play a pivotal role in HER2-positive breast carcinogenesis
Authors found that elevated levels of pSphK1 were positive correlation with high expression of S1P, which in turn promoted metastasis of TNBC through S1P/S1PR3/Notch signaling pathway.
SphK1 may be novel targets for inhibiting lymph node metastasis in esophageal squamous cell carcinoma.
Butyrate and bioactive proteolytic form of Wnt-5a regulate colonic epithelial proliferation and spatial development
Immunohistochemistry of xenograft tumors showed significant enhancement of caspase-3 cleavage and suppression of Ki67 and phospho-EGFR by the drug combination, but SphK1 downregulation occurred only in MDA-MB-468 tumors, so is unlikely to be integral to treatment efficacy
Data show that sphingosine kinase 1 (SPHK1) was significantly upregulated in oral squamous cell carcinoma (OSCC) tissues and low levels of sphingosine-1-phosphate lyase 1 (SGPL1) mRNA correlated with a worse overall survival, and that sphingosine-1-phosphate receptor 2 (S1PR2) is over-expressed in a subset of tumours, which in part mediates sphingosine 1-phosphate (S1P)-induced migration of OSCC cells.
SphK1 expression regulates the early stage of colon carcinogenesis and tumor growth, thus inhibition of SphK1 may be an effective strategy for colon cancer chemoprevention.
the blockage of SPHK1 activity to attenuate autophagy may be a promising strategy for the prevention and treatment of patocellular carcinoma
Results indicate the involvement of sphingosine kinase-1 (SphK1) in the invasiveness of oral squamous cell carcinoma (OSCC) and in unfavorable prognosis.
Sphk1 induced NF-kappaB-p65 activation, increased expression of cyclin D1, shortened the cell division cycle, and thus promoted proliferation of breast epithelial cells.
Sphingosine kinase 1 has distinct roles in the activation of Kupffer cells (KCs) and hepatic stellate cells (HSCs) in liver fibrosis. Mechanistically, SphK1 in KCs mediates CCL2 secretion, and SphK1 in HSCs upregulates CCR2 by downregulation of miR-19b-3p.
vascular transcriptome analysis shows that S1P pathway is critical in the regulation of vascular function in AngII-induced hypertension, although Sphk1 may have opposing roles in the regulation of vasoconstriction and endothelium-dependent vasorelaxation.
The cell division gene PCNA was significantly overexpressed in SK2(-/-) cells, suggesting a cross regulation between sphingosine kinases and Ceramide glucosyltransferase.
Studied role of microglial cells in inflammation via a Toll-like receptor 2 (TLR2)-->sphingosine kinase 1 (Sphk1)-->pro-inflammatory cytokine pathway in cerebral ischemia/reperfusion (I/R).
SphK1 is involved in maladaptive hypertrophy and we propose that heart failure might be an additional direct target for therapeutic intervention with SphK1 inhibitors.
These results suggest that SphK1 expression plays a pivotal role in the early stages of colon carcinogenesis
the recruitment of Sphk1 to sphingosine-enriched endocytic vesicles and the generation of sphingosine-1-phosphate facilitate membrane trafficking along the endosomal pathway.
SK1 activation is renoprotective via induction of autophagy in the fibrotic process
donor islets from mice deficient in Sphk1 KO contain a reduced number of resident intraislet vascular endothelial cells. The main product of Sphk1, sphingosine-1-phosphate, controls the migration of intraislet endothelial cells in vitro. In vivo, Sphk1 knockout islets have an impaired ability to cure diabetes compared with wild-type controls.
Sphingosine kinase 1 worsens pancreatic cancer peritoneal carcinomatosis by stimulation of proliferation of cancer cells.
These results highlight the importance of sphingosine and its conversion to sphingosine-1-phosphate by SphK1 in endocytic membrane trafficking.
Melatonin-treated cells also exhibited an inhibition of the SphK1/S1P axis. Antifibrogenic effect of SphK1 inhibition was confirmed by treatment of LX2 cells with PF543. Abrogation of the lipid signaling pathway by the indole reveals novel molecular pathways that may account for the protective effect of melatonin in liver fibrogenesis.
These findings suggest that the inhibitory effect of these plant extracts on the activation of AGEs/RAGE/SphK1 signaling pathway in db/db diabetic mice kidney is a novel mechanism by which they exert renoprotective effects in diabetic nephropathy.
Keratinocyte-specific deletion of Traf2, but not Sphk1 deficiency, disrupted TNF mediated NF-kappaB and MAP kinase signalling and caused epidermal hyperplasia and psoriatic skin inflammation.
SphK1 dependent PKC-delta activation plays an important role in promoting NF-kappaB activation and inflammatory response in acute liver failure, and inhibition of PKC-delta activation might be a potential therapeutic strategy for this disease.
The protein encoded by this gene catalyzes the phosphorylation of sphingosine to form sphingosine-1-phosphate (S1P), a lipid mediator with both intra- and extracellular functions. Intracellularly, S1P regulates proliferation and survival, and extracellularly, it is a ligand for cell surface G protein-coupled receptors. This protein, and its product S1P, play a key role in TNF-alpha signaling and the NF-kappa-B activation pathway important in inflammatory, antiapoptotic, and immune processes. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.
, sphingosine kinase 1
, sphingosine kinase I
, SK 1
, SPK 1