WordNet

an enzyme that catalyzes the conversion of a proenzyme to an active enzyme
the basic unit of money in Papua New Guinea

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/08/13 05:10:06」(JST)

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sphingosine kinase 2
Identifiers
Symbol	SPHK2
Entrez	56848
HUGO	18859
OMIM	607092
RefSeq	NM_020126
UniProt	Q9NRA0
Other data
EC number	2.7.1.91
Locus	Chr. 19 q13.2

Sphingosine kinase (SphK) is a conserved lipid kinase that catalyzes formation sphingosine-1-phosphate (S1P) from the precursor sphingolipid sphingosine. Sphingolipid metabolites, such as ceramide, sphingosine and sphingosine-1-phosphate, are lipid second messengers involved in diverse cellular processes. There are two forms of SphK, SphK1 and SphK2. SphK1 is found in the cytosol of eukaryotic cells, and migrates to the plasma membrane upon activation. SphK2 is localized to the nucleus.

Function

S1P has been shown to regulate diverse cellular processes. It has been characterized as a lipid signaling molecule with dual function. On one hand, it exerts its actions extracellularly by binding to the five different S1P receptors that couple to a variety of G-proteins to regulate diverse biological functions, ranging from cell growth and survival to effector functions, such as proinflammatory mediator synthesis. On the other hand, it appears to act as an intracellular second messenger,^[1] although the relevant molecular target(s) to which it binds within cells remains to be discovered. In any case, a role of S1P in various functions of cells and tissues is established, including regulation of cell survival and motility, angiogenesis, and inflammatory responses. Sphingosine kinases (SphKs) types 1 and 2, the two enzymes identified so far in mammals that produce S1P by ATP-dependent phosphorylation of sphingosine, have therefore received considerable interest.^[2]

Sphingolipid metabolism

Sphingolipids are ubiquitous membrane constituents of all eukaryotic cells. In general, the term sphingolipid (SL) refers to any of a number of lipids consisting of a head group attached to the 1-OH of ceramide (Cer). Ceramides consist of a sphingoid base, commonly referred to as a long-chain base (LCB), which is N-acylated. De novo synthesis of LCBs begins with the condensation of palmitoyl CoA with serine, forming 3-ketosphinganine (Fig. 1). This product is then reduced to sphinganine, also known as dihydrosphingosine (dihydro-Sph; 2-amino-l,3-dihydroxy-octadecane). A 14– to 26-carbon fatty acid chain is then added in an amide linkage with the 2-amino group, forming dihydroceramide (dihydro-Cer). A head group, such as phosphocholine or a carbohydrate, can now be added to the 1-OH, forming a sphingolipid, although most sphingolipids of higher eukaryotes contain further modifications of the LCB.^[3]

de novo synthesis

Popular culture

During "100,000 Airplanes", a third season episode of The West Wing, sphingosine kinase is fictitiously described as "the enzyme believed to control all signal pathways to cancer growth." Learning of it inspires the protagonist of the series, President Josiah Bartlet, to consider launching an Apollo program to cure cancer.

References

^ Olivera A, Spiegel S (April 2001). "Sphingosine kinase: a mediator of vital cellular functions". Prostaglandins Other Lipid Mediat. 64 (1–4): 123–34. doi:10.1016/S0090-6980(01)00108-3. PMID 11324702.
^ Billich A, Bornancin F, Mechtcheriakova D, Natt F, Huesken D, Baumruker T (October 2005). "Basal and induced sphingosine kinase 1 activity in A549 carcinoma cells: function in cell survival and IL-1beta and TNF-alpha induced production of inflammatory mediators". Cell. Signal. 17 (10): 1203–17. doi:10.1016/j.cellsig.2004.12.005. PMID 16038795.
^ Maceyka M, Milstien S, Spiegel S (September 2005). "Sphingosine kinases, sphingosine-1-phosphate and sphingolipidomics". Prostaglandins Other Lipid Mediat. 77 (1–4): 15–22. doi:10.1016/j.prostaglandins.2004.09.010. PMID 16099387.

External links

sphingosine kinase at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 心筋障害のバイオマーカーとしてのトロポニンおよびクレアチンキナーゼ troponins and creatine kinase as biomarkers of cardiac injury
2. 未分化リンパ腫キナーゼ（ALK）融合癌遺伝子陽性非小細胞肺癌 anaplastic lymphoma kinase alk fusion oncogene positive non small cell lung cancer
3. ホスホリラーゼbキナーゼ欠損症 phosphorylase b kinase deficiency
4. ホスホグリセリン酸キナーゼ欠損症およびホスホグリセリン酸ムターゼ欠損症 phosphoglycerate kinase deficiency and phosphoglycerate mutase deficiency
5. 複合免疫不全 combined immunodeficiencies

English Journal

Sphingosine kinase 2 prevents the nuclear translocation of sphingosine 1-phosphate receptor-2 and tyrosine 416 phosphorylated c-Src and increases estrogen receptor negative MDA-MB-231 breast cancer cell growth: The role of sphingosine 1-phosphate receptor-4.

Ohotski J1, Rosen H2, Bittman R3, Pyne S1, Pyne NJ4.Author information 1Cell Biology Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, United Kingdom.2The Scripps Research Institute, Department of Chemistry, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, United States.3Department of Chemistry and Biochemistry, Queens College, The City University of New York, Flushing, NY 11367-1597, United States.4Cell Biology Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, United Kingdom. Electronic address: n.j.pyne@strath.ac.uk.AbstractWe demonstrate that pre-treatment of estrogen receptor negative MDA-MB-231 breast cancer cells containing ectopically expressed HA-tagged sphingosine 1-phosphate receptor-2 (S1P2) with the sphingosine kinase 1/2 inhibitor SKi (2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole) or the sphingosine kinase 2 selective inhibitor (R)-FTY720 methyl ether (ROMe) or sphingosine kinase 2 siRNA induced the translocation of HA-tagged S1P2 and Y416 phosphorylated c-Src to the nucleus of these cells. This is associated with reduced growth of HA-tagged S1P2 over-expressing MDA-MB-231 cells. Treatment of HA-S1P2 over-expressing MDA-MB-231 cells with the sphingosine 1-phosphate receptor-4 (S1P4) antagonist CYM50367 or with S1P4 siRNA also promoted nuclear translocation of HA-tagged S1P2. These findings identify for the first time a signaling pathway in which sphingosine 1-phosphate formed by sphingosine kinase 2 binds to S1P4 to prevent nuclear translocation of S1P2 and thereby promote the growth of estrogen receptor negative breast cancer cells.
Cellular signalling.Cell Signal.2014 May;26(5):1040-7. doi: 10.1016/j.cellsig.2014.01.023. Epub 2014 Jan 29.
We demonstrate that pre-treatment of estrogen receptor negative MDA-MB-231 breast cancer cells containing ectopically expressed HA-tagged sphingosine 1-phosphate receptor-2 (S1P2) with the sphingosine kinase 1/2 inhibitor SKi (2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole) or the sphingosine kinas
PMID 24486401

High-density lipoprotein induces cyclooxygenase-2 expression and prostaglandin I-2 release in endothelial cells through sphingosine kinase-2.

Xiong SL1, Liu X, Yi GH.Author information 1You Country People's Hospital, Zhuzhou, 412300, Hunan, China, xslyxry@163.com.AbstractHigh-density lipoprotein (HDL) has a significant cardioprotective effects. HDL induces cyclooxygenase-2 (COX-2) expression and prostacyclin I-2 (PGI-2) release in vascular endothelial cells, which contributes to its anti-atherogenic effects. However, the underlying mechanisms are not fully understood. In the present study, we observed that HDL-stimulated COX-2 expression and PGI-2 production in human umbilical vein endothelial cells (HUVECs) in a time- and dose-dependent manner. These effects triggered by HDL were inhibited by pertussis toxin (PTX), protein kinase C (PKC) inhibitor GF109203X, and ERK inhibitor PD98059, suggesting that Gαi/Gαo-coupled GPCR, PKC, and ERK pathways are involved in HDL-induced COX-2/PGI-2 activation. More importantly, we found that silencing of sphingosine kinase 2 (SphK-2) also blocked HDL-induced COX-2/PGI-2 activation. In addition, HDL-activated SphK-2 phosphorylation accompanied by increased S1P level in the nucleus. Our ChIP data demonstrated that SphK-2 is associated with CREB at the COX-2 promoter region. Collectively, these results indicate that HDL induces COX-2 expression and PGI-2 release in endothelial cells through activation of PKC, ERK1/2, and SphK-2 pathways. These findings implicate a novel mechanism underlying anti-atherothrombotic effects of HDL.
Molecular and cellular biochemistry.Mol Cell Biochem.2014 Apr;389(1-2):197-207. doi: 10.1007/s11010-013-1941-y. Epub 2014 Jan 3.
High-density lipoprotein (HDL) has a significant cardioprotective effects. HDL induces cyclooxygenase-2 (COX-2) expression and prostacyclin I-2 (PGI-2) release in vascular endothelial cells, which contributes to its anti-atherogenic effects. However, the underlying mechanisms are not fully understoo
PMID 24385109

Hippocampal lipoprotein lipase regulates energy balance in rodents.

Picard A1, Rouch C2, Kassis N2, Moullé VS1, Croizier S3, Denis RG3, Castel J2, Coant N1, Davis K4, Clegg DJ4, Benoit SC5, Prévot V3, Bouret S6, Luquet S2, Le Stunff H1, Cruciani-Guglielmacci C1, Magnan C1.Author information 1Université Paris Diderot, Sorbonne Paris Cité, BFA, EAC 4413 CNRS, Case courrier 7126, 4, rue Marie Andrée Lagroua Weill-Hallé, F-75205 Paris Cedex 13, France.2Université Paris Diderot, Sorbonne Paris Cité, BFA, EAC 4413 CNRS, Case courrier 7126, 4, rue Marie Andrée Lagroua Weill-Hallé, F-75205 Paris Cedex 13, France ; Centre National de la Recherche Scientifique-CNRS EAC 4413, F-75205 Paris, France.3Jean-Pierre Aubert Research Center, Development and Plasticity of the Postnatal Brain, INSERM U837, 59045 Lille Cedex, France.4Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.5Department of Psychiatry, University of Cincinnati, Cincinnati, OH, USA.6Jean-Pierre Aubert Research Center, Development and Plasticity of the Postnatal Brain, INSERM U837, 59045 Lille Cedex, France ; The Saban Research Institute, Neuroscience Program, Children's Hospital Los Angeles, University of Southern California, Los Angeles, USA.AbstractBrain lipid sensing is necessary to regulate energy balance. Lipoprotein lipase (LPL) may play a role in this process. We tested if hippocampal LPL regulated energy homeostasis in rodents by specifically attenuating LPL activity in the hippocampus of rats and mice, either by infusing a pharmacological inhibitor (tyloxapol), or using a genetic approach (adeno-associated virus expressing Cre-GFP injected into Lpl (lox/lox) mice). Decreased LPL activity by either method led to increased body weight gain due to decreased locomotor activity and energy expenditure, concomitant with increased parasympathetic tone (unchanged food intake). Decreased LPL activity in both models was associated with increased de novo ceramide synthesis and neurogenesis in the hippocampus, while intrahippocampal infusion of de novo ceramide synthesis inhibitor myriocin completely prevented body weight gain. We conclude that hippocampal lipid sensing might represent a core mechanism for energy homeostasis regulation through de novo ceramide synthesis.
Molecular metabolism.Mol Metab.2013 Nov 20;3(2):167-76. doi: 10.1016/j.molmet.2013.11.002. eCollection 2014.
Brain lipid sensing is necessary to regulate energy balance. Lipoprotein lipase (LPL) may play a role in this process. We tested if hippocampal LPL regulated energy homeostasis in rodents by specifically attenuating LPL activity in the hippocampus of rats and mice, either by infusing a pharmacologic
PMID 24634821

Japanese Journal

Pachastrissamine (jaspine B) and its stereoisomers inhibit sphingosine kinases and atypical protein kinase C.

Yoshimitsu Yuji,Oishi Shinya,Miyagaki Jun,Inuki Shinsuke,Ohno Hiroaki,Fujii Nobutaka
Bioorganic & medicinal chemistry 19(18), 5402-5408, 2011-09-15
… Sphingosine kinases (SphKs) are oncogenic enzymes that regulate the critical balance between ceramide and sphingosine-1-phosphate. … Inhibitory effects were profiled against protein kinase C (PKC) isoforms by in vitro experiments. …
NAID 120003386631

SKI-II, an Inhibitor of Sphingosine Kinase, Ameliorates Antigen-Induced Bronchial Smooth Muscle Hyperresponsiveness, but Not Airway Inflammation, in Mice

CHIBA Yoshihiko,TAKEUCHI Hiroki,SAKAI Hiroyasu,MISAWA Miwa
Journal of pharmacological sciences 114(3), 304-310, 2010-11-20
NAID 10029890451

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「kinase」

sphingosine kinase 1
Identifiers
Symbol	SPHK1
Entrez	8877
HUGO	11240
OMIM	603730
RefSeq	NM_182965
UniProt	Q9NYA1
Other data
EC number	2.7.1.91
Locus	Chr. 17 q25.2

Search
PMC	articles
PubMed	articles
NCBI	proteins

sphinganine kinase
Identifiers
EC number	2.7.1.91
CAS number	50864-48-7
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Gene Ontology	AmiGO / EGO
Search
PMC	articles
PubMed	articles
NCBI	proteins

　　[★] キナーゼカイネースリン酸化酵素 phosphoenzyme phosphotransferase 　

[pmid11324702-1] Olivera A, Spiegel S (April 2001). "Sphingosine kinase: a mediator of vital cellular functions". Prostaglandins Other Lipid Mediat. 64 (1–4): 123–34. doi:10.1016/S0090-6980(01)00108-3. PMID 11324702.

[pmid16038795-2] Billich A, Bornancin F, Mechtcheriakova D, Natt F, Huesken D, Baumruker T (October 2005). "Basal and induced sphingosine kinase 1 activity in A549 carcinoma cells: function in cell survival and IL-1beta and TNF-alpha induced production of inflammatory mediators". Cell. Signal. 17 (10): 1203–17. doi:10.1016/j.cellsig.2004.12.005. PMID 16038795.

[pmid16099387-3] Maceyka M, Milstien S, Spiegel S (September 2005). "Sphingosine kinases, sphingosine-1-phosphate and sphingolipidomics". Prostaglandins Other Lipid Mediat. 77 (1–4): 15–22. doi:10.1016/j.prostaglandins.2004.09.010. PMID 16099387.

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sphingosine kinase