2.7.1.91: sphingosine kinase
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For detailed information about sphingosine kinase, go to the full flat file.
Word Map on EC 2.7.1.91
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2.7.1.91
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sphingosine-1-phosphate
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1-phosphate
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sphingolipids
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ceramide
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endothelial
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sirnas
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necrosis
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agonist
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metastasis
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artery
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erk
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phospholipase
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fingolimod
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fibrosis
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lymphocyte
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protein-coupled
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sphingomyelinase
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tnf
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pulmonary
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leukemia
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sphingomyelin
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anti-apoptotic
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s1p-induced
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stat3
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pertussis
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mapks
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pro-apoptotic
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mitogen
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sclerosis
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pkc
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rheostat
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signal-regulated
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caspase-3
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pro-survival
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platelet-derived
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lysophospholipids
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cardioprotective
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phytosphingosine
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drug development
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lymphopenia
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egress
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glucosylceramide
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medicine
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fumonisins
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s1p-mediated
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dihydroceramide
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mitogenesis
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pdgf-induced
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ceramide-induced
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lysophosphatidic
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fcepsilonri
- 2.7.1.91
- sphingosine-1-phosphate
- 1-phosphate
- sphingolipids
- ceramide
- endothelial
- sirnas
- necrosis
- agonist
- metastasis
- artery
- erk
- phospholipase
- fingolimod
- fibrosis
- lymphocyte
-
protein-coupled
- sphingomyelinase
- tnf
- pulmonary
- leukemia
- sphingomyelin
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anti-apoptotic
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s1p-induced
- stat3
- pertussis
- mapks
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pro-apoptotic
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mitogen
- sclerosis
- pkc
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rheostat
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signal-regulated
- caspase-3
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pro-survival
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platelet-derived
- lysophospholipids
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cardioprotective
- phytosphingosine
- drug development
- lymphopenia
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egress
- glucosylceramide
- medicine
- fumonisins
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s1p-mediated
- dihydroceramide
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mitogenesis
-
pdgf-induced
-
ceramide-induced
-
lysophosphatidic
- fcepsilonri
Reaction
Synonyms
dihydrosphingosine kinase, kinase, dihydrosphingosine (phosphorylating), kinase, sphingosine (phosphorylating), More, SGK, SK, SK-1, SK-2, SK1, SK2, sphinganine kinase, sphingoid base kinase, sphingosine kinase, sphingosine kinase 1, sphingosine kinase 2, sphingosine kinase type 1, sphingosine kinase type 2, sphingosine kinase-1, sphingosine kinase-2, SPHK, SPHK-1, SPHK1, SPHK1a, SPHK1b, SPHK2, SPK
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medicine
involved in signal transduction by TRAF2, tumor necrosis factor-alpha receptor-associated factor 2
medicine
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isozyme SPHK1 is a potential therapeutic target in the treatment of inflammatory and autoimmune diseases
medicine
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targeting SPHK may provide a novel therapeutic tool to treat bronchial asthma
medicine
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89% of human colon cancer samples tested stain positively for SphK1, whereas normal colon mucosa has negative or weak staining. Adenomas have higher expression of SphK1 versus normal mucosa, and colon cancers with metastasis have higher expression of SphK1 than those without metastasis
medicine
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adenovirus-mediated SPK1 gene transfer promotes recovery of the surgically damaged mesothelial cell layer and prevents postoperative peritoneal adhesion formation
medicine
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after 4 weeks of systemic ovalbumin sensitization and local airway challenge, airway responsiveness increases less in SphK1-/- compared with wild-type mice, whereas pulmonary vascular responsiveness is greatly increased and does not differ between strains. Acute lung inflammation leads to an increase in eosinophils and mRNA expression for sphingosine 1-phosphate phosphatase 2 and sphingosine 1-phosphate lyase in lungs of wild-type but not SphK1-/- mice. After repetitive allergen exposure for 8 weeks, airway responsiveness is not augmented in SphK1-/- or wild-type mice, but pulmonary vascular responsiveness is increased in both strains, with significantly higher vascular responsiveness in SphK1-/- mice compared with that seen in wild-type mice
medicine
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chronic activation of SPHK1-S1P signalling results in both pathological cardiac remodelling through reactive oxygen species mediated by S1P3 and favourable cardioprotective effects
medicine
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in a mouse model of streptozotocin-induced diabetic nephropathy, isoform Sk1 and connective tisuue grwoth factor CTGF are upregulated in podocytes. In Sk1 deficient mice, exacerbation of diesease is detected by increased albuminuria and CTGF expression when compared to wild-type
medicine
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in a murine collagen-induced arthritis model, prophylactic i.p. administration of SphK1 siRNA significantly reduces the incidence, disease severity, and articular inflammation compared with control siRNA recipients. Treatment of SphK1 siRNA also down-regulates serum levels of sphingosine 1-phosphate, IL-6, TNF-alpha, IFN-gamma, and IgG2a anticollagen Ab. Ex vivo analysis demonstrates significant suppression of collagen-specific proinflammatory/Th1 cytokine IL-6, TNF-alpha, IFN-gamma release in SphK siRNA-treated mice. Mice received with SphK2 siRNA develop more aggressive disease, higher serum levels of IL-6, TNF-alpha, and IFN-gamma, and proinflammatory cytokine production to collagen in vitro when compared with control siRNA recipients
medicine
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In the azoxymethane murine model of colon cancer, SphK1 and sphingosine 1-phosphate are significantly elevated in colon cancer tissues compared to normal mucosa. Blood levels of sphingosine 1-phosphate are higher in mice with colon cancers than in those without cancers. SphK1-/- mice subjected to azoxymethane have significantly less aberrant crypt foci formation and significantly reduced colon cancer development
medicine
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isoform Sk1 expression is increased in the podocytes of kidney sections of patients with diabetic nephropathy
medicine
isoform SphK1 protein and mRNA levels are higher in clinical tissue samples of patients with non-Hodgkin lymphomas than in reactive lymphoid hyperplasias, with a clear trend towards increasng levels with increasing clinicla grade
medicine
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levels of SPHK1mRNA and protein are higher in gastric cancer cell lines than in normal gastric epithelial cells. SPHK1 protein level is up-regulated in gastric cancer lesions compared with that in the paired adjacent noncancerous tissues. Gastric cancer tissues from 65.7% of patients reveals high level of SPHK1protein expression in contrast to the undetectable or marginally detectable expression of SPHK1 in the adjacent noncancerous gastric tissues. Significantly different expression levels of SPHK1 are found in patients at different clinical stages. Patients with higher SPHK1expression have shorter overall survival time, whereas those with lower SPHK1 expression survive longer
medicine
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patients with breast cancer that express higher CerS2 or 4 mRNA levels tend to show no changes in sphingosine kinase 1 levels, and likewise patients that express no change in CerS2 or CerS4 mRNA levels tend to express higher levels of sphingosine kinase 1. Results suggest an important role for the CerS genes in breast cancer etiology or diagnosis
medicine
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pharmacologic SphK1 inhibition with B-5354c sensitizes LNCaP and PC-3 cells to docetaxel and camptothecin, respectively. In vivo, camptothecin and B-5354c alone display a limited effect on tumor growth in PC-3 cells, whereas in combination there is a synergy of effect on tumor size with a significant increase in the ceramide to sphingosine 1-phosphate sphingolipid ratio
medicine
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sphingosine analogue FTY720, which is activated by phosphorylation specifically by SPHK2, mediates apoptotic signaling of cultured synovial fibroblasts
medicine
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SphK1 inhibition by docetaxel is a two-step process involving an initial loss of enzyme activity followed by a decrease in SphK1 gene expression. Both pharmacological and siRNA-mediated SphK1 inhibition leads to a four-fold decrease in the docetaxel IC50 dose
medicine
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SPHK1in astrocytoma cell lines is elevated at both mRNA and protein levels, and the SPHK1 mRNA and protein are significantly up-regulated by up to 6.8- and 40fold, respectively, in primary astrocytomas compared with those in the adjacent noncancerous brain tissues. 41.2% of paraffin-embedded archival astrocytoma biopsies exhibit high expression of SPHK1. The up-regulation of SPHK1 is significantly correlated with the histologic grade of astrocytoma and patients with high SPHK1 level exhibit shorter survival time
medicine
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synthesis of shingosine kinase substrates as sphingosine 1-phosphate receptor prodrugs, with varying activities at the five sphingosine 1-phosphate receptors
medicine
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synthesis of shingosine kinase substrates as sphingosine 1-phosphate receptor prodrugs, with varying activities at the five sphingosine 1-phosphate receptors. Substrate (2R)-2-amino-2-[5-(4-octylphenyl)-1H-imidazol-2-yl]propan-1-ol causes lymphopenia for more than 20h
medicine
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the growth of SphK2-deficient MCF-7 breast tumor xenografts is markedly delayed when compared with controls. Infiltration of macrophages in SphK2-deficient and control tumors is comparable. Tumor-associated macrophages from SphK2-deficient tumors display a pronounced anti-tumor phenotype, showing an increased expression of pro-inflammatory markers/mediators such as NO, TNF-alpha, IL-12 and MHCII and a low expression of anti-inflammatory IL-10 and CD206
medicine
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the synovial fluid levels of sphingosine 1-phosphate are significantly higher in patients with rheumatoid arthritis than in those with osteoarthritis. Small chronic increases in SK1 activity in the endothelial cells enhance the ability of the cells to support inflammation and undergo angiogenesis, and sensitize the cells to inflammatory cytokines. The SK1 signaling pathway is activated in rheumatoid arthritis
medicine
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treatment of wild-type and Sphk1 null mouse hearts by ischaemic postconditioning. Postconditioning consisting of 5 s of ischaemia and 5 s of reperfusion for three cycles after the index ischaemia, protects hearts against ischaemia/reperfusion injury, recovery of left ventricular developed pressure and maximum velocity of increase or decrease of left ventricular pressure are elevated and left ventricular end-diastolicpressure is decreased, infarction size is reduced from 40% in the control group to 29% of the risk area in the postconditioning group. Phosphorylation of Akt and extracellular signal-regulated kinases is increased at 10 min of reperfusion. The protection induced by postconditioning is abolished in Sphk1 null mouse hearts
medicine
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when sphingosine kinase 1 is deleted in Sandhoff disease mice, a prototypical neuronopathic lysosomal storage disorder, a milder disease course occurs, with decreased proliferation of glial cells and less-pronounced astrogliosis. A similar result of milder disease course and reduced astroglial proliferation is obtained by deletion of the gene for the S1P(3) receptor, a G protein-coupled receptor enriched in astrocytes
medicine
the expression level and properties of N-terminal 86 amino-acid isoform variant of sphingosine kinase 1, SK1b, in prostate cancer cells reduce its sensitivity to proteasomal degradation induced by 2-(4-hydroxyanilino)-4-(4-chlorophenyl)thiazole in comparison to isoform SK1a. The reduced sensitivity of SK1b to proteasomal degradation in response to 2-(4-hydroxyanilino)-4-(4-chlorophenyl)thiazole results in specific changes in ceramide and S1P levels that lead to apoptosis of androgen-sensitive but not androgen-independent LNCaP prostate cancer cells
medicine
sphingosine kinase-1 expression inversely correlates with survival after immune checkpoint inhibitor (ICI) therapy in melanoma tumors. Downregulation of sphingosine kinase-1 improves the efficacy of ICI therapy in various cancer models