Any feedback?
Information on EC 2.7.1.91 - sphingosine kinase and Organism(s) Mus musculus and UniProt Accession Q8CI15
for references in articles please use BRENDA:EC2.7.1.91Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
2.7.1.91 sphingosine kinaseIUBMB Comments
The enzyme is involved in the production of sphingolipid metabolites. It phosphorylates various sphingoid long-chain bases, such as sphingosine, D-erythro-dihydrosphingosine (sphinganine), phytosphingosine (4-hydroxysphinganine), 4-hydroxy-8-sphingenine, 4,8-sphingadienine and D-threo-dihydrosphingosine and L-threo-dihydrosphingosine. The exact substrate range depends on the species.
Specify your search results
Word Map
- 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
-
anti-apoptotic
-
s1p-induced
- stat3
- pertussis
- mapks
-
pro-apoptotic
-
mitogen
- sclerosis
- pkc
-
rheostat
-
signal-regulated
- caspase-3
-
pro-survival
-
platelet-derived
- lysophospholipids
-
cardioprotective
- phytosphingosine
- drug development
- lymphopenia
-
egress
- glucosylceramide
- medicine
- fumonisins
-
s1p-mediated
- dihydroceramide
-
mitogenesis
-
pdgf-induced
-
ceramide-induced
-
lysophosphatidic
- fcepsilonri
The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
sphk1, sphingosine kinase, sphk2, sphingosine kinase 1, sphingosine kinase-1, sphingosine kinase 2, sphk-1, sphingosine kinase-2, sphk1a, sphingosine kinase type 1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
sphingosine kinase-1
is a substrate for the cysteine protease cathepsin B
SPHK1
dihydrosphingosine kinase
-
-
-
-
kinase, dihydrosphingosine (phosphorylating)
-
-
-
-
kinase, sphingosine (phosphorylating)
-
-
-
-
SK
-
-
-
-
sphinganine kinase
sphingoid base kinase
-
-
-
-
SPHK
SPHK2
additional information
SPHK
-
-
-
-
additional information
-
the enzyme belongs to the subfamily of diacylglyceride kinases DAGKs
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
ATP + a sphingoid base = ADP + a sphingoid base 1-phosphate
Asp177 in C4 domain of isozyme SK1a is important for sphingosine substrate recognition
ATP + a sphingoid base = ADP + a sphingoid base 1-phosphate
catalytic mechanism, the catalytic domain contains the C1-C5 sequence stretches and the ATP-binding site
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phospho group transfer
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
ATP:sphingoid base 1-phosphotransferase
The enzyme is involved in the production of sphingolipid metabolites. It phosphorylates various sphingoid long-chain bases, such as sphingosine, D-erythro-dihydrosphingosine (sphinganine), phytosphingosine (4-hydroxysphinganine), 4-hydroxy-8-sphingenine, 4,8-sphingadienine and D-threo-dihydrosphingosine and L-threo-dihydrosphingosine. The exact substrate range depends on the species.
CAS REGISTRY NUMBER
COMMENTARY
50864-48-7
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + D-erythro-sphingosine
ADP + D-erythro-sphingosine 1-phosphate
-
-
-
?
ATP + (2R)-2-amino-2-[5-(4-octylphenyl)-1H-imidazol-2-yl]propan-1-ol
ADP + (2R)-2-amino-2-[5-(4-octylphenyl)-1H-imidazol-2-yl]propyl dihydrogen phosphate
-
-
product is a sphingosine 1-phosphate receptor prodrug
-
?
ATP + 2-amino-2-[4-(4-octylphenyl)-1,3-oxazol-2-yl]propan-1-ol
ADP + 2-amino-2-[4-(4-octylphenyl)-1,3-oxazol-2-yl]propyl dihydrogen phosphate
-
-
product is a sphingosine 1-phosphate receptor prodrug
-
?
ATP + 2-amino-2-[5-(4-octylphenyl)-1,2,4-oxadiazol-3-yl]propan-1-ol
ADP + 2-amino-2-[5-(4-octylphenyl)-1,2,4-oxadiazol-3-yl]propyl dihydrogen phosphate
-
-
product is a sphingosine 1-phosphate receptor prodrug
-
?
ATP + D-(+)-erythro-sphinganine
ADP + D-(+)-erythro-sphinganine 1-phosphate
-
-
-
?
ATP + FTY720
ADP + FTY720 1-phosphate
immunomodulatory drug, high activity with isozyme SPHK2, lower activity with isozyme SPHK1
-
-
?
ATP + sphingosine
ADP + sphingosine 1-phosphate
-
-
-
?
ATP + sphingosine
ADP + sphingosine 1-phosphate
involved in diverse biological functions
-
-
?
ATP + D-erythro-sphingosine
ADP + D-erythro-sphingosine 1-phosphate
-
-
-
?
ATP + sphinganine
ADP + sphinganine 1-phosphate
-
involved in regulation of GTP cyclohydrolase I and 6(r)-5,6,7,8-tetrahydrobiopterin
-
-
?
ATP + sphinganine
ADP + sphinganine 1-phosphate
-
the lipid phosphate acts as a pleiotropic agent in cell signalling pathways, enzyme is involved in the sphingomyelid pathway, overview
-
-
?
ATP + sphingosine
ADP + sphingosine 1-phosphate
-
-
short-living product S1P is a bioactive lipid mediator in diverse cellular processes, e.g. regulation of cell differentiation, motility, and apoptosis both extracellularly via S1P family receptors and intracellularly
-
?
ATP + sphingosine
ADP + sphingosine 1-phosphate
-
-
sphingosine 1-phosphate is a potent bioactive sphingolipid, sphingolipid metabolism, overview
-
ir
ATP + sphingosine
ADP + sphingosine 1-phosphate
-
isozymes SPHK1 is about 100fold more active than isozyme SPHK2
-
-
?
additional information
?
-
-
sphinganine 1-phosphate acts as an extracellular mediator by binding to specific members of the EDG-family of G-protein coupled receptors, and intracellularly as a messenger
-
-
?
additional information
?
-
-
the enzyme is involved in many cellular processes, e.g. mast cell activation during inflammation, immunoactivation via intracellular Ca2+ and receptor activation, angiogenesis and control of cell adhesion molecule expression, anti-apoptosis
-
-
?
additional information
?
-
-
sphingosine kinase-mediated signalling plays a role in the innate and adaptive immune responses by altering migration of dendritic cells
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
ATP + D-erythro-sphingosine
ADP + D-erythro-sphingosine 1-phosphate
-
-
-
?
ATP + sphingosine
ADP + sphingosine 1-phosphate
involved in diverse biological functions
-
-
?
ATP + D-erythro-sphingosine
ADP + D-erythro-sphingosine 1-phosphate
-
-
-
?
ATP + sphinganine
ADP + sphinganine 1-phosphate
-
involved in regulation of GTP cyclohydrolase I and 6(r)-5,6,7,8-tetrahydrobiopterin
-
-
?
ATP + sphinganine
ADP + sphinganine 1-phosphate
-
the lipid phosphate acts as a pleiotropic agent in cell signalling pathways, enzyme is involved in the sphingomyelid pathway, overview
-
-
?
ATP + sphingosine
ADP + sphingosine 1-phosphate
-
-
short-living product S1P is a bioactive lipid mediator in diverse cellular processes, e.g. regulation of cell differentiation, motility, and apoptosis both extracellularly via S1P family receptors and intracellularly
-
?
ATP + sphingosine
ADP + sphingosine 1-phosphate
-
-
sphingosine 1-phosphate is a potent bioactive sphingolipid, sphingolipid metabolism, overview
-
ir
additional information
?
-
-
sphinganine 1-phosphate acts as an extracellular mediator by binding to specific members of the EDG-family of G-protein coupled receptors, and intracellularly as a messenger
-
-
?
additional information
?
-
-
the enzyme is involved in many cellular processes, e.g. mast cell activation during inflammation, immunoactivation via intracellular Ca2+ and receptor activation, angiogenesis and control of cell adhesion molecule expression, anti-apoptosis
-
-
?
additional information
?
-
-
sphingosine kinase-mediated signalling plays a role in the innate and adaptive immune responses by altering migration of dendritic cells
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
Ca2+-dependent calmodulin binding of recombinant wild-type and mutant enzymes
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2R,3S,4E)-N-methyl-5-(4-pentylphenyl)-2-aminopent-4-ene-1,3-diol
-
i.e. SK1-I, BML-258, isotype-specific SphK1 inhibitor. SK1-I markedly reduces the tumor growth rate of glioblastoma xenografts, inducing apoptosis and reducing tumor vascularization, and enhances the survival of mice harboring LN229 intracranial tumors
2-(p-hydroxyanilino)-4-(p-chlorophenyl) thiazole
-
the inhibition of SPHK affects acute eosinophilic inflammation induced in antigen-challenged mouse model
K145
i.e. (5E)-3-(2-aminoethyl)-5-[3-(4-butoxyphenyl)propylidene]-1,3-thiazolidine-2,4-dione, isoform SphK2-selective inhibitor
-
sphingosine kinase inhibitor
-
can influence co-stimulatory molecules (CD40, CD80, CD86 and MHC class II) and cytokine production (IL-12 and IL-10) in murine bone marrow-derived dendritic cells. Sphingosine kinase inhibitor significantly inhibits co-stimulatory molecules in dendritic cells. Sphingosine kinase inhibitor suppresses IL-12 production by dendritic cells and IFN-gamma production by T cells
-
N,N-dimethylsphingosine
-
the inhibition of SPHK affects acute eosinophilic inflammation induced in antigen-challenged mouse model
N,N-dimethylsphingosine
-
suppression of SphK1 by its inhibitor, N,N-dimethylsphingosine, or siRNA results in decreased mRNA expression of TNF-alpha, IL-1beta and iNOS and release of TNF-alpha and nitric oxide in lipopolysaccharid-activated microglia
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Calmodulin
Ca2+-dependent binding of recombinant wild-type and mutant enzymes
lipopolysaccharide
-
increases Sk1 transcription which is accompanied by increased SK activity and generation of sphingosine 1-phosphate. Sphingosine 1-phosphate is able to cause increases in COX-2 and PGE2 levels in RAW cells
N-(1,3-dihydroxyisopropyl)-2-hexyl-3-oxo-decanamide
-
i.e. K6PC-5, activates SphK in a dose-dependent manner. K6PC-5 induces mobilization in hairless mouse epidermis. Both dimethylsphingosine and dihydroxysphingosine, SphK inhibitors, and transfection of SphK1-siRNA blocks K6PC-5-induced increases in intracellular Ca2+ concentration
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.01
sphingosine
pH 7.4, 37°C, recombinant wild-type enzyme and mutant E181Q
additional information
additional information
kinetics, recombinant wild-type and mutant enzymes
-
additional information
additional information
-
kinetics, recombinant wild-type and mutant enzymes
-
additional information
additional information
kinetics, isozymes SPHK1 and SPHK2
-
additional information
additional information
kinetics, isozymes SPHK1 and SPHK2
-
additional information
additional information
-
kinetics, isozymes SPHK1 and SPHK2
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
Vmax of different splicing variants of both isozymes
additional information
Vmax of different splicing variants of both isozymes
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
in airway epithelium of a mouse asthmatic model, both SphK and MUC5AC expression are increased and proteins co-localize
-
from bone marrow. N,N-dimethyl-D-erythro-sphingosine inhibits osteoclastogenesis a sphingosine kinase independently of sphingosine kinase
-
SPHK1, exclusively in the acrosome, spermatozoa contain 5 sphingosine 1-phosphate receptors
additional information
higher activity of isozyme SPHK1, low activity of isozyme SPHK2
high activity of isozyme SPHK2, low activity of isozyme SPHK1
high activity of isozyme SPHK1, low activity of isozyme SPHK2
additional information
tissue distribution of isozyme SPHK1 and isozyme SPHK2 expression and activity, overview
additional information
tissue distribution of isozyme SPHK1 and isozyme SPHK2 expression and activity, overview
additional information
-
tissue distribution of isozyme SPHK1 and isozyme SPHK2 expression and activity, overview
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
additional information
-
activation of Gq protein-coupled receptors induces a profound, rapid and long-lasting translocation of isoform SphK1 to the plasma membrane
additional information
unlike isozyme SK1, isozyme SK2 does not translocate the membrane fraction following calmodulin binding
-
additional information
unlike isozyme SK1, isozyme SK2 does not translocate the membrane fraction following calmodulin binding
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
the interconversion of sphingosine and sphingosine1-phosphate is mediated in the forward direction by sphingosine kinase and in the opposing way by specific sphingosine 1-phosphate phosphatases and less specific lipid phosphate phosphatases
physiological function
malfunction
single SK1 and SK2 knockout mouse models show little phenotypic change
metabolism
the interconversion of sphingosine and sphingosine1-phosphate is mediated in the forward direction by sphingosine kinase and in the opposing way by specific sphingosine 1-phosphate phosphatases and less specific lipid phosphate phosphatases
physiological function
additional information
malfunction
activation-dependent increase of intracellular Ca2+ concentration, degranulation (release of alpha and dense granules), integrin alphaIIbbeta3 activation, and aggregation are all significantly increased in enzyme-deficient sphk1-/- platelets compared with wild-type sphk1+/+ platelets. While platelet adhesion and thrombus formation under arterial shear rates are significantly augmented in Sphk1-deficient platelets, bleeding time and blood count are unaffected in sphk1-/- mice
malfunction
single SK1 and SK2 knockout mouse models show little phenotypic change
malfunction
isoform SPHK1 deletion reduces endoplasm reticulum stress and alleviates inflammation response in hydrogen peroxide-treated cells
physiological function
D-erythro-sphingosine 1-phosphate elicits numerous cellular responses via a family of G-protein coupled receptors, as well as intracellular effectors
physiological function
sphingosine kinase 1 is a powerful negative regulator of platelet function counteracting degranulation, aggregation, and thrombus formation. In mast cells, intracellular Ca2+ is rapidly and transiently increased by spingosine kinase 1. Sphingosine 1-phosphate mobilizes intracellular Ca2+ in mast cells in an inositol triphosphate-dependent manner. In other cell types, sphingosine kinases regulate intracellular Ca2+ by influencing voltage-gated Ca2+ channels or by activating the store-operated calcium entry. Sphingosine kinases and sphingosine 1-phosphate further regulate platelet formation by megakaryopoiesis. They are effective by upregulating Src family kinases in megakaryocytes. Megakyocytes express the S1P multifunctional receptor S1pr1, and S1P signaling is an important prerequisite for proper thrombopoesis
physiological function
isofom SPHK1 upregulation, induced by hydrogen peroxide, is responsible for cerebral IR injury through inducing endoplasm reticulum stress and inflammation response in a manner working through the nuclear factor-kappaB signaling pathway
physiological function
-
a short period of ischaemic postconditioning protects wild-type mouse hearts against ischaemia/reperfusion injury. The cardiac protection induced by postcondition is abrogated in SphK1-KO mouse hearts
physiological function
-
activation of Gq protein-coupled receptors induces a profound, rapid and long-lasting translocation of isoform SphK1 to the plasma membrane. Classical Gq signalling pathways, or phosphorylation at Ser225, phospholipase D and Ca2+/calmodulin are not involved in M3 receptor-induced SphK1 translocation in HEK-293 cells. Translocation is associated with Sphingosine 1-phosphate receptor internalization, which is dependent on catalytic activity of SphK1 and sphingosine 1-phosphate receptor binding and thus results from S1P receptor cross-activation
physiological function
-
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
physiological function
-
in cardiac fibroblasts, sphingosine 1-phosphate increases alpha-smooth muscle actin and collagen expression in a S1P2 receptor- and Rho-kinase-dependent manner. TGF-beta increases sphingosine kinase 1 expression and activity. TGF-beta-stimulated collagen production is inhibited by SphK1 or S1P2 siRNA, a SphK inhibitor, and an anti-S1P monoclonal antibody
physiological function
-
in contrast to wild-type mice, Sphk1-/- mice show markedly enhanced pulmonary edema formation in response to lipopolysaccharide and PAR-1 activation. Increased SPHK1 activity and decreased intracellular S1P concentration precede the onset of lung microvascular barrier recovery. Knockdown of SPHK1 decreases basal sphingosine 1-phoshate production and Rac1 activity but increases basal endothelial permeability. In SPHK1-depleted cells, PAR-1 activation fails to induce Rac1 activation but augments RhoA activation and endothelial hyperpermeability response. Knockdown of S1P1 receptor in endothelial cells also enhances the increase in endothelial permeability following PAR-1 activation. Sphingosine 1-phosphate treatment of Sphk1-/- lungs or SPHK1-deficient endothelial cells restores endothelial barrier function
physiological function
-
in SPHK1-deficient mice, absence of the enzyme abrogates MCP-1 production induced in dermal microvascular endothelial cells upon treatment with thrombin or PAR-1 activating peptide
physiological function
-
isoform SphK1 deficient SphK1-/- mice are much more susceptible to lipopolysaccharide-induced lung injury than wild-type. Overexpression of wild-type SphK1 in lungs protects SphK1-/- mice from lung injury and attenuates the severity of the response to lipopolysaccharide. Overexpression of a ShpK1 kinase-dead mutant in SphK1-/- mouse lungs further exacerbates the response to lipopolysaccharide as well as the extent of lung injury. Wild-type isoform SphK2 overexpression also fails to provide protection and augments the degree of lipopolysaccharide-induced lung injury
physiological function
-
knock-down of SK1 using siRNA is able to inhibit the TNF but not the lipopolysaccharide inflammatory response. Knock-down of SK1 enhances both TNF- and lipopolysaccharide-induced apoptosis
physiological function
-
mice depleted of isoform SK1 have increased vascular leakiness, whereas mice transgenic for SK1 in endothelial cells show attenuation of leakiness
physiological function
-
siRNA of SPHK1 inhibits cell proliferation of v-Src-transformed NIH-3T3 cells
physiological function
-
SK1-/- mice treated with dextran sulfate sodium have significantly less blood loss, weight loss, colon shortening, colon histological damage, and splenomegaly than wild-type mice. SK1-/- mice have no systemic inflammatory response, and wild-type but not SK1-/- mice treated with dextran sulfate sodium have significant increases in blood sphingosine 1-phosphate levels, colon SK1 message and activity, and colon neutrophilic infiltrate. Unlike wild-type mice, SK1-/- mice fail to show colonic COX-2 induction despite an exaggerated TNF-alpha response
physiological function
-
SphK activity, SphK1 protein content and sphingosine 1-phosphate formation are enhanced in myoblasts that became confluent as well as in differentiating cells. Enforced expression of SphK1 reduces the myoblast proliferation rate, enhances the expression of myogenic differentiation markers and anticipates the onset of differentiated muscle phenotype. Down-regulation of SphK1 by specific silencing byRNA interference or overexpression of a catalytically inactive SphK1, significantly increases cell growth and delays the beginning of myogenesis. Exogenous addition of sphingosine 1-phosphate rescues the biological processes. Stimulation of myogenesis in SphK1-overexpressing myoblasts is abrogated by treatment with short interfering RNA specific for S1P2 receptor
physiological function
-
SphK1-/- mice subjected to azoxymethane treatment have significantly less aberrant crypt foci formation and significantly reduced colon cancer development than wild-type
physiological function
-
SPHK1-transgenic mice overexpress SPHK1 in diverse tissues, with a nearly 20fold increase in enzymatic activity. The transgenic mice grow normally with normal blood chemistry, cell counts, heart rate, and blood pressure. Transgenic mice with high but not low expression levels of SPHK1 develop progressive myocardial degeneration and fibrosis, with upregulation of embryonic genes, elevated RhoA and Rac1 activity, stimulation of Smad3 phosphorylation, and increased levels of oxidative stress markers. Treatment of juvenile transgenic mice with pitavastatin, or deletion of S1P3, a major myocardial S1P receptor subtype both inhibit cardiac fibrosis with concomitant inhibition of SPHK1-dependent Smad-3 phosphorylation. In addition, the anti-oxidant N-2-mercaptopropyonylglycine, also inhibits cardiac fibrosis. In in vivo ischaemia/reperfusion injury, the size of myocardial infarct is 30% decreased in SPHK1-transgenic mice compared with wild-type mice
physiological function
-
suppression of SphK1 by its inhibitor, N,N-dimethylsphingosine, or siRNA results in decreased mRNA expression of TNF-alpha, IL-1beta and iNOS and release of TNF-alpha and nitric oxide in lipopolysaccharid-activated microglia
physiological function
-
the knockdown of SphK1 by siRNA in mast cells inhibits several signaling mechanisms and effector functions, triggered by FcepsilonRI stimulation and including Ca2+ signals, NFkappaB activation, degranulation, cytokine/chemokine, and eicosanoid production. Silencing SphK2 has no effect at all. Silencing SPHK1 in vivo, in different strains of mice, strongly inhibits mast cell-mediated anaphylaxis, including inhibition of vascular permeability, tissue mast cell degranulation, changes in temperature, and serum histamine and cytokine levels, whereas silencing SPHK2 has no effect and the mice develop anaphylaxis. In mast cells derived from SPHK1-/- and SPHK2-/- mice, the calcium response and degranulation, triggered by FcepsilonRI-cross-linking, is not different from that triggered in wild-type cells. IgE-mediated anaphylaxis in the knockout mice shows similar levels in temperature changes and serum histamine to that from wild-type mice
physiological function
-
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
physiological function
-
wild-type mesangial cells respond to staurosporine with increased DNA fragmentation and caspase-3 processing, which is enhanced in SK1-/- cells. SK2-/- cells are highly resistant to staurosporine-induced apoptosis. The basal phosphorylation and activity of the anti-apoptotic protein kinase B and of its substrate Bad are decreased in SK1-/- but not in SK2-/- cells. Upon staurosporine treatment, phosphorylation of protein kinase B and Bad decrease in wild-type and SK1-/- cells, but remain high in SK2-/- cells. The anti-apoptotic Bcl-XL is significantly upregulated in SK2-/- cells
physiological function
-
renal ischemia-reperfusion injury induces isoform SK1, but not SK2, in the kidneys. Knockout or pharmacological inhibition of isoform SK1 increases injury after renal ischemia-reperfusion injury
physiological function
D-erythro-sphingosine 1-phosphate elicits numerous cellular responses via a family of G-protein coupled receptors, as well as intracellular effectors
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). SPHK1_MOUSE
382
0
42443
Swiss-Prot
other Location (Reliability: 5)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
lesser amounts of immunoreactive protein migrate in the 45-48 kDa range
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D175N/D177N
site-directed mutagenesis, less than 5% of wild-type enzyme activity
D177N
site-directed mutagenesis, less than 10% of wild-type enzyme activity
S225A
the mutation prevents ERK1/2-mediated phosphorylation and membrane localization of SK1
G213E/L219A
site-directed mutagenesis, the mutant is catalytically inactive
G82D
-
catalytically inactive. Overexpression in myoblast cells significantly increases cell growth and delays the beginning of myogenesis
L219A
site-directed mutagenesis, the mutant shows about 38% of wild-type activity
additional information
additional information
-
site-directed mutagenesis at Cys-4 and Cys-5 residues results in increased sphingosine kinase activity
additional information
site-directed mutagenesis at Cys-4 and Cys-5 residues results in increased sphingosine kinase activity
additional information
generation of enzyme-deficient sphk1-/- mice, platelets from sphk1-/- mice do not show spontaneous or activation-dependent formation of platelet-leukocyte aggregates and a significantly increased activation-dependent ATP release and in vitro thrombus formation compared with the wild-type
additional information
-
site-directed mutagenesis at Cys-4 and Cys-5 residues results in increased sphingosine kinase activity
additional information
site-directed mutagenesis at Cys-4 and Cys-5 residues results in increased sphingosine kinase activity
additional information
construction of catalytically inactive deletion mutants DELTA1-227 and DELTA227-618
additional information
construction of catalytically inactive deletion mutants DELTA1-227 and DELTA227-618
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
isozymes SPHK1 and SPHK2, expression in HEK293 cells as EGFP-fusion proteins
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
isoform SPHK1 expression is significantly elevated after exposure to hydrogen peroxide
both lipopolysaccharide and thrombin increase mouse lung microvascular permeability and result in a delayed activation of SPHK1 that is coupled to the onset of restoration of pulmonary microvessel permeability
-
dihydrotestosterone triggers cell growth in steroid-deprived MC-3T3 cells, associated with a rapid stimulation of isoform SphK1 and activation of both Akt and ERK signaling pathways. This mechanism relies on functional androgen receptor/PI3K/Akt nongenotropic signaling as pharmacological antagonists can block SphK1 stimulation by dihydrotestosterone and its consequences. SphK1 inhibition also blocks cell proliferation, while ERK inhibition has no impact
-
inhibition of protein kinase C-alpha, signal transducers and activators of transcription 3 and c-Jun NH2-terminal kinase inhibition suppresses SPHK1 expression in v-Src-transformed NIH-3T3 cells, whereas their overexpression increases SPHK1 mRNA. Modulation of AUF1 and HuR by their overexpression or siRNA reveals that SPHK1 mRNA in v-Src- and mock-NIH3T3 is regulated reciprocally by these factors
-
treatment with lipopolysaccharid causes significantly enhances isoform SphK1 expression within 6 h, which declines back to baseline levels by 24 h. Expression of isoform SphK2 is gradually induced following lipopolysaccharide treatment and is elevated within 24 h
-
treatment with lipopolysaccharide increases the SphK1 mRNA and protein expression in microglia leading to altered expression and production of proinflammatory cytokines and nitric oxide. Suppression of SphK1 by its inhibitor, N, N-dimethylsphingosine, or siRNA results in decreased mRNA expression of TNF-alpha, IL-1beta and iNOS and release of TNF-alpha and nitric oxide in lipopolysaccharid-activated microglia
-
v-Src-transfected cells show both increased SPHK1 mRNA and enzyme activity. Inhibition of protein kinase C-alpha, signal transducers and activators of transcription 3 and c-Jun NH2-terminal kinase inhibition suppresses SPHK1 expression in v-Src-transformed NIH-3T3 cells, whereas their overexpression increases SPHK1 mRNA. Modulation of AUF1 and HuR by their overexpression or siRNA reveals that SPHK1 mRNA in v-Src- and mock-NIH3T3 is regulated reciprocally by these factors
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
medicine
-
targeting SPHK may provide a novel therapeutic tool to treat bronchial asthma
medicine
-
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
-
chronic activation of SPHK1-S1P signalling results in both pathological cardiac remodelling through reactive oxygen species mediated by S1P3 and favourable cardioprotective effects
medicine
-
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
-
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
-
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
-
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
-
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
-
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
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Mazurek, N.; Megidish, T.; Hakomori, S.; Igarashi, Y.
Regulatory effect of phorbol esters on sphingosine kinase in BALB/C 3T3 fibroblasts (variant A31): Demonstration of cell type-specific response--a preliminary note
Biochem. Biophys. Res. Commun.
198
1-9
1994
Mus musculus
Ancellin, N.; Colmont, C.; Su, J.; Li, Q.; Mittereder, N.; Chae, S.S.; Stefansson, S.; Liau, G.; Hla, T.
Extracellular export of sphingosine kinase-1 enzyme. Sphingosine 1-phosphate generation and the induction of angiogenic vascular maturation
J. Biol. Chem.
277
6667-6675
2002
Mus musculus
Vann, L.R.; Payne, S.G.; Edsall, L.C.; Twitty, S.; Spiegel, S.; Milstien, S.
Involvement of sphingosine kinase in TNF-alpha-stimulated tetrahydrobiopterin biosynthesis in C6 glioma cells
J. Biol. Chem.
277
12649-12656
2002
Mus musculus
Liu, H.; Sugiura, M.; Nava, V.E.; Edsall, L.C.; Kono, K.; Poulton, S.; Milstien, S.; Kohama, T.; Spiegel, S.
Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform
J. Biol. Chem.
275
19513-19520
2000
Mus musculus (Q9JIA7), Mus musculus, Homo sapiens (Q9NRA0), Homo sapiens
Fukuda, Y.; Kihara, A.; Igarashi, Y.
Distribution of sphingosine kinase activity in mouse tissues: contribution of SPHK1
Biochem. Biophys. Res. Commun.
309
155-160
2003
Mus musculus
Kee, T.H.; Vit, P.; Melendez, A.J.
Sphingosine kinase signalling in immune cells
Clin. Exp. Pharmacol. Physiol.
32
153-161
2005
Arabidopsis thaliana, Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Tetrahymena pyriformis
Yokota, S.; Taniguchi, Y.; Kihara, A.; Mitsutake, S.; Igarashi, Y.
Asp177 in C4 domain of mouse sphingosine kinase 1a is important for the sphingosine recognition
FEBS Lett.
578
106-110
2004
Mus musculus (Q8CI15), Mus musculus
Baumruker, T.; Bornancin, F.; Billich, A.
The role of sphingosine and ceramide kinases in inflammatory responses
Immunol. Lett.
96
175-185
2005
Homo sapiens, Mus musculus
Billich, A.; Bornancin, F.; Devay, P.; Mechtcheriakova, D.; Urtz, N.; Baumruker, T.
Phosphorylation of the immunomodulatory drug FTY720 by sphingosine kinases
J. Biol. Chem.
278
47408-47415
2003
Mus musculus (O88885), Mus musculus (Q9JIA7), Mus musculus, Homo sapiens (Q9NRA0), Homo sapiens (Q9NYA1), Homo sapiens
Matsumoto, K.; Banno, Y.; Murate, T.; Akao, Y.; Nozawa, Y.
Localization of sphingosine kinase-1 in mouse sperm acrosomes
J. Histochem. Cytochem.
53
243-247
2005
Mus musculus
Kono, Y.; Nishiuma, T.; Nishimura, Y.; Kotani, Y.; Okada, T.; Nakamura, S.; Yokoyama, M.
Sphingosine kinase 1 regulates differentiation of human and mouse lung fibroblasts mediated by TGF-beta1
Am. J. Respir. Cell Mol. Biol.
37
395-404
2007
Mus musculus (Q8CI15), Mus musculus, Homo sapiens (Q9NRA0), Homo sapiens (Q9NYA1), Homo sapiens
Zemann, B.; Kinzel, B.; Mueller, M.; Reuschel, R.; Mechtcheriakova, D.; Urtz, N.; Bomancin, F.; Baumruker, T.; Billich, A.
Sphingosine kinase type 2 is essential for lymphopenia induced by the immunomodulatory drug FTY720
Blood
107
1454-1458
2006
Mus musculus (Q9JIA7)
Jin, Z.Q.; Zhang, J.; Huang, Y.; Hoover, H.E.; Vessey, D.A.; Karliner, J.S.
A sphingosine kinase 1 mutation sensitizes the myocardium to ischemia/reperfusion injury
Cardiovasc. Res.
76
41-50
2007
Mus musculus
Soldi, R.; Mandinova, A.; Venkataraman, K.; Hla, T.; Vadas, M.; Pitson, S.; Duarte, M.; Graziani, I.; Kolev, V.; Kacer, D.; Kirov, A.; Maciag, T.; Prudovsky, I.
Sphingosine kinase 1 is a critical component of the copper-dependent FGF1 export pathway
Exp. Cell Res.
313
3308-3318
2007
Mus musculus (Q8CI15)
Taha, T.A.; El-Alwani, M.; Hannun, Y.A.; Obeid, L.M.
Sphingosine kinase-1 is cleaved by cathepsin B in vitro: Identification of the initial cleavage sites for the protease
FEBS Lett.
580
6047-6054
2006
Mus musculus (Q8CI15), Rattus norvegicus (Q91V26), Homo sapiens (Q9NYA1)
Leclerq, T.M.; Pitson, S.M
Cellular signalling by sphingosine kinase and sphingosine 1-phosphate
IUBMB Life
58
467-472
2006
Mus musculus (Q8CI15), Homo sapiens (Q9NRA0), Homo sapiens (Q9NYA1)
Kihara, A.; Anada, Y.; Igarashi, Y.
Mouse sphingosine kinase isoforms SPHK1a and SPHK1b differ in enzymatic traits including stability, localization, modification, and oligomerization
J. Biol. Chem.
281
4532-4539
2006
Mus musculus, Mus musculus (Q8CI15)
Kusner, D.J.; Thompson, C.R.; Melrose, N.A.; Pitson, S.M.; Obeid, L.M.; Iyer, S.S.
The localization and activity of sphingosine kinase 1 are coordinately regulated with actin cytoskeletal dynamics in macrophages
J. Biol. Chem.
282
23147-23162
2007
Mus musculus (Q8CI15), Homo sapiens (Q9NYA1)
Blondeau, N.; Lai, Y.; Tyndall, S.; Popolo, M.; Topalkara, K.; Pru, J.K.; Zhang, L.; Kim, H.H.; Liao, J.K.; Ding, K.; Waeber, C.
Distribution of sphingosine kinase activity and mRNA in rodent brain
J. Neurochem.
103
509-517
2007
Mus musculus (Q9JIA7)
Kohno, M.; Momoi, M.; Oo, M.L.; Paik, J.H.; Lee, Y.M.; Venkataraman, K.; Ai, Y.; Ristimaki, A.OP.; Fyrst, H.; Sano, H.; Rosenberg, D.; Saba, J.D.; Proia, R.L.; Hla1, T.
Intracellular role for sphingosine kinase 1 in intestinal adenoma cell proliferation
Mol. Cell. Biol.
26
7211-7223
2006
Mus musculus (Q8CI15), Homo sapiens (Q9NYA1)
Nishiuma, T.; Nishimura, Y.; Okada, T.; Kuramoto, E.; Kotani, Y.; Jahangeer, S.; Nakamura, S.
Inhalation of sphingosine kinase inhibitor attenuates airway inflammation in asthmatic mouse model
Am. J. Physiol. Lung Cell. Mol. Physiol.
294
L1085-L1093
2008
Mus musculus
Jung, I.D.; Lee, J.S.; Kim, Y.J.; Jeong, Y.I.; Lee, C.M.; Lee, M.G.; Ahn, S.C.; Park, Y.M.
Sphingosine kinase inhibitor suppresses dendritic cell migration by regulating chemokine receptor expression and impairing p38 mitogen-activated protein kinase
Immunology
121
533-544
2007
Mus musculus
Jung, I.D.; Lee, J.S.; Kim, Y.J.; Jeong, Y.I.; Lee, C.M.; Baumruker, T.; Billlich, A.; Banno, Y.; Lee, M.G.; Ahn, S.C.; Park, W.S.; Han, J.; Park, Y.M.
Sphingosine kinase inhibitor suppresses a Th1 polarization via the inhibition of immunostimulatory activity in murine bone marrow-derived dendritic cells
Int. Immunol.
19
411-426
2007
Mus musculus
Kim, H.J.; Lee, Y.; Chang, E.J.; Kim, H.M.; Hong, S.P.; Lee, Z.H.; Ryu, J.; Kim, H.H.
Suppression of osteoclastogenesis by N,N-dimethyl-D-erythro-sphingosine: a sphingosine kinase inhibition-independent action
Mol. Pharmacol.
72
418-428
2007
Mus musculus
Wadgaonkar, R.; Patel, V.; Grinkina, N.; Romano, C.; Liu, J.; Zhao, Y.; Sammani, S.; Garcia, J.; Natarajan, V.
Differential regulation of sphingosine kinases 1 and 2 in lung injury
Am. J. Physiol. Lung Cell Mol. Physiol.
296
L603-L613
2009
Mus musculus
Martin, C.; Lafosse, J.M.; Malavaud, B.; Cuvillier, O.
Sphingosine kinase-1 mediates androgen-induced osteoblast cell growth
Biochem. Biophys. Res. Commun.
391
669-673
2009
Mus musculus
Ter Braak, M.; Danneberg, K.; Lichte, K.; Liphardt, K.; Ktistakis, N.T.; Pitson, S.M.; Hla, T.; Jakobs, K.H.; Heringdorf, D.M.
Ga(q)-mediated plasma membrane translocation of sphingosine kinase-1 and cross-activation of S1P receptors
Biochim. Biophys. Acta
1791
357-370
2009
Mus musculus
Hofmann, L.P.; Ren, S.; Schwalm, S.; Pfeilschifter, J.; Huwiler, A.
Sphingosine kinase 1 and 2 regulate the capacity of mesangial cells to resist apoptotic stimuli in an opposing manner
Biol. Chem.
389
1399-1407
2008
Mus musculus
Foss, F.W.; Mathews, T.P.; Kharel, Y.; Kennedy, P.C.; Snyder, A.H.; Davis, M.D.; Lynch, K.R.; Macdonald, T.L.
Synthesis and biological evaluation of sphingosine kinase substrates as sphingosine-1-phosphate receptor prodrugs
Bioorg. Med. Chem.
17
6123-6136
2009
Homo sapiens, Mus musculus
Li, X.; Stankovic, M.; Bonder, C.S.; Hahn, C.N.; Parsons, M.; Pitson, S.M.; Xia, P.; Proia, R.L.; Vadas, M.A.; Gamble, J.R.
Basal and angiopoietin-1-mediated endothelial permeability is regulated by sphingosine kinase-1
Blood
111
3489-3497
2008
Homo sapiens, Mus musculus
Kapitonov, D.; Allegood, J.C.; Mitchell, C.; Hait, N.C.; Almenara, J.A.; Adams, J.K.; Zipkin, R.E.; Dent, P.; Kordula, T.; Milstien, S.; Spiegel, S.
Targeting sphingosine kinase 1 inhibits Akt signaling, induces apoptosis, and suppresses growth of human glioblastoma cells and xenografts
Cancer Res.
69
6915-6923
2009
Homo sapiens, Mus musculus
Jin, Z.Q.; Karliner, J.S.; Vessey, D.A.
Ischaemic postconditioning protects isolated mouse hearts against ischaemia/reperfusion injury via sphingosine kinase isoform-1 activation
Cardiovasc. Res.
79
134-140
2008
Mus musculus
Gellings Lowe, N.; Swaney, J.S.; Moreno, K.M.; Sabbadini, R.A.
Sphingosine-1-phosphate and sphingosine kinase are critical for transforming growth factor-beta-stimulated collagen production by cardiac fibroblasts
Cardiovasc. Res.
82
303-312
2009
Mus musculus
Takuwa, N.; Ohkura, S.; Takashima, S.; Ohtani, K.; Okamoto, Y.; Tanaka, T.; Hirano, K.; Usui, S.; Wang, F.; Du, W.; Yoshioka, K.; Banno, Y.; Sasaki, M.; Ichi, I.; Okamura, M.; Sugimoto, N.; Mizugishi, K.; Nakanuma, Y.; Ishii, I.; Takamura, M.; Kaneko, S.; Kojo, S.; Satouchi, K.; Mitumori, K.; Chun, J.; Takuwa Y.
S1P3-mediated cardiac fibrosis in sphingosine kinase 1 transgenic mice involves reactive oxygen species
Cardiovasc. Res.
85
484-493
2010
Mus musculus
Tauseef, M.; Kini, V.; Knezevic, N.; Brannan, M.; Ramchandaran, R.; Fyrst, H.; Saba, J.; Vogel, S.M.; Malik, A.B.; Mehta, D.
Activation of sphingosine kinase-1 reverses the increase in lung vascular permeability through sphingosine-1-phosphate receptor signaling in endothelial cells
Circ. Res.
103
1164-1172
2008
Mus musculus
Snider, A.J.; Kawamori, T.; Bradshaw, S.G.; Orr, K.A.; Gilkeson, G.S.; Hannun, Y.A.; Obeid, L.M.
A role for sphingosine kinase 1 in dextran sulfate sodium-induced colitis
FASEB J.
23
143-152
2009
Mus musculus
Kawamori, T.; Kaneshiro, T.; Okumura, M.; Maalouf, S.; Uflacker, A.; Bielawski, J.; Hannun, Y.A.; Obeid, L.M.
Role for sphingosine kinase 1 in colon carcinogenesis
FASEB J.
23
405-414
2009
Homo sapiens, Mus musculus
Wu, Y.P.; Mizugishi, K.; Bektas, M.; Sandhoff, R.; Proia, R.L.
Sphingosine kinase 1/S1P receptor signaling axis controls glial proliferation in mice with Sandhoff disease
Hum. Mol. Genet.
17
2257-2264
2008
Mus musculus
Billich, A.; Urtz, N.; Reuschel, R.; Baumruker, T.
Sphingosine kinase 1 is essential for proteinase-activated receptor-1 signalling in epithelial and endothelial cells
Int. J. Biochem. Cell Biol.
41
1547-1555
2009
Homo sapiens, Mus musculus
Haberberger, R.V.; Tabeling, C.; Runciman, S.; Gutbier, B.; Koenig, P.; Andratsch, M.; Schuette, H.; Suttorp, N.; Gibbins, I.; Witzenrath, M.
Role of sphingosine kinase 1 in allergen-induced pulmonary vascular remodeling and hyperresponsiveness
J. Allergy Clin. Immunol.
124
933-41.e1-9
2009
Mus musculus
Meacci, E.; Nuti, F.; Donati, C.; Cencetti, F.; Farnararo, M.; Bruni, P.
Sphingosine kinase activity is required for myogenic differentiation of C2C12 myoblasts
J. Cell. Physiol.
214
210-220
2008
Mus musculus
Lai, W.Q.; Irwan, A.W.; Goh, H.H.; Melendez, A.J.; McInnes, I.B.; Leung, B.P.
Distinct roles of sphingosine kinase 1 and 2 in murine collagen-induced arthritis
J. Immunol.
183
2097-2103
2009
Mus musculus
Pushparaj, P.N.; Manikandan, J.; Tay, H.K.; Hng, S.C.; Kumar, S.D.; Pfeilschifter, J.; Huwiler, A.; Melendez, A.J.
Sphingosine kinase 1 is pivotal for Fc epsilon RI-mediated mast cell signaling and functional responses in vitro and in vivo
J. Immunol.
183
221-227
2009
Mus musculus
Hong, J.H.; Youm, J.K.; Kwon, M.J.; Park, B.D.; Lee, Y.M.; Lee, S.I.; Shin, D.M.; Lee, S.H.
K6PC-5, a direct activator of sphingosine kinase 1, promotes epidermal differentiation through intracellular Ca2+ signaling
J. Invest. Dermatol.
128
2166-2178
2008
Homo sapiens, Mus musculus
Ren, S.; Babelova, A.; Moreth, K.; Xin, C.; Eberhardt, W.; Doller, A.; Pavenstaedt, H.; Schaefer, L.; Pfeilschifter, J.; Huwiler, A.
Transforming growth factor-beta2 upregulates sphingosine kinase-1 activity, which in turn attenuates the fibrotic response to TGF-beta2 by impeding CTGF expression
Kidney Int.
76
857-867
2009
Homo sapiens, Mus musculus
Nayak, D.; Huo, Y.; Kwang, W.X.; Pushparaj, P.N.; Kumar, S.D.; Ling, E.A.; Dheen, S.T.
Sphingosine kinase 1 regulates the expression of proinflammatory cytokines and nitric oxide in activated microglia
Neuroscience
166
132-144
2009
Mus musculus
Sobue, S.; Murakami, M.; Banno, Y.; Ito, H.; Kimura, A.; Gao, S.; Furuhata, A.; Takagi, A.; Kojima, T.; Suzuki, M.; Nozawa, Y.; Murate, T.
v-Src oncogene product increases sphingosine kinase 1 expression through mRNA stabilization: alteration of AU-rich element-binding proteins
Oncogene
27
6023-6033
2008
Mus musculus
Hammad, S.M.; Crellin, H.G.; Wu, B.X.; Melton, J.; Anelli, V.; Obeid, L.M.
Dual and distinct roles for sphingosine kinase 1 and sphingosine 1 phosphate in the response to inflammatory stimuli in RAW macrophages
Prostaglandins Other Lipid Mediat.
85
107-114
2008
Mus musculus
Kono, Y.; Nishiuma, T.; Okada, T.; Kobayashi, K.; Funada, Y.; Kotani, Y.; Jahangeer, S.; Nakamura, S.I.; Nishimura, Y.
Sphingosine kinase 1 regulates mucin production via ERK phosphorylation
Pulm. Pharmacol. Ther.
23
36-42
2010
Homo sapiens, Mus musculus
Park, S.W.; Kim, M.; Kim, M.; DAgati, V.D.; Lee, H.T.
Sphingosine kinase 1 protects against renal ischemia-reperfusion injury in mice by sphingosine-1-phosphate1 receptor activation
Kidney Int.
80
1315-1327
2011
Homo sapiens, Mus musculus
Muenzer, P.; Schmid, E.; Walker, B.; Fotinos, A.; Chatterjee, M.; Rath, D.; Vogel, S.; Hoffmann, S.M.; Metzger, K.; Seizer, P.; Geisler, T.; Gawaz, M.; Borst, O.; Lang, F.
Sphingosine kinase 1 (Sphk1) negatively regulates platelet activation and thrombus formation
Am. J. Physiol. Cell Physiol.
307
C920-C927
2014
Mus musculus (Q8CI15), Mus musculus C57BL/6 (Q8CI15)
Baker, D.; Pham, T.; Sparks, M.
Structure and catalytic function of sphingosine kinases: analysis by site-directed mutagenesis and enzyme kinetics
Biochim. Biophys. Acta
1831
139-146
2013
Mus musculus (Q8CI15), Mus musculus (Q9JIA7), Homo sapiens (Q9NRA0), Homo sapiens (Q9NYA1)
Zhang, M.; Zhou, D.; Ouyang, Z.; Yu, M.; Jiang, Y.
Sphingosine kinase 1 promotes cerebral ischemia-reperfusion injury through inducing ER stress and activating the NF-kappaB signaling pathway
J. Cell. Physiol.
235
6605-6614
2020
Mus musculus (Q8CI15)
Worrell, B.L.; Brown, A.M.; Santos, W.L.; Bevan, D.R.
In silico characterization of structural distinctions between isoforms of human and mouse sphingosine kinases for accelerating drug discovery
J. Chem. Inf. Model.
59
2339-2351
2019
Mus musculus (Q8CI15), Mus musculus (Q9JIA7), Mus musculus, Homo sapiens (Q9NRA0), Homo sapiens (Q9NYA1), Homo sapiens
EXTERNAL LINKS (specific for EC-Number 2.7.1.91)
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
