View source for Sphingosine kinase

{{enzyme
| Name = sphinganine kinase
| EC_number = 2.7.1.91
| CAS_number = 50864-48-7
| IUBMB_EC_number = 2/7/1/91
| GO_code = 0008481
| image = 
| width = 
| caption = 
}}
{{infobox protein
|Name= [[sphingosine kinase 1]]
|caption= Sphingosine kinase 1, hexamer, Human
|image= 3vzd.jpg
|width= 270
|HGNCid=11240
|Symbol=[[sphingosine kinase 1|SPHK1]]
|AltSymbols=
|EntrezGene=8877
|OMIM=603730
|RefSeq=NM_182965
|UniProt=Q9NYA1
|PDB=
|ECnumber= 2.7.1.91
|Chromosome=17
|Arm=q
|Band=25.2
|LocusSupplementaryData=
}}
{{infobox protein
|Name=[[SPHK2|sphingosine kinase 2]]
|caption=
|image=
|width=
|HGNCid=18859
|Symbol=[[SPHK2]]
|AltSymbols=
|EntrezGene=56848
|OMIM=607092
|RefSeq=NM_020126
|UniProt=Q9NRA0
|PDB=
|ECnumber= 2.7.1.91
|Chromosome=19
|Arm=q
|Band=13.2
|LocusSupplementaryData=
}}

'''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 signaling|lipid second messengers]] involved in diverse cellular processes.  There are two forms of SphK, [[SPHK1|SphK1]] and [[SPHK2|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 [[GPCR|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]],<ref name="pmid11324702">{{cite journal |vauthors=Olivera A, Spiegel S | title = Sphingosine kinase: a mediator of vital cellular functions | journal = Prostaglandins Other Lipid Mediat. | volume = 64 | issue = 1–4 | pages = 123–34 |date=April 2001 | pmid = 11324702 | doi = 10.1016/S0090-6980(01)00108-3| url = | issn = }}</ref> although the relevant molecular target(s) to which it binds within cells remains to be discovered. The 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 [[adenosine triphosphate|ATP]]-dependent [[phosphorylation]] of [[sphingosine]], have therefore received considerable interest.<ref name="pmid16038795">{{cite journal |vauthors=Billich A, Bornancin F, Mechtcheriakova D, Natt F, Huesken D, Baumruker T | title = 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 | journal = Cell. Signal. | volume = 17 | issue = 10 | pages = 1203–17 |date=October 2005 | pmid = 16038795 | doi = 10.1016/j.cellsig.2004.12.005 | url = | issn = }}</ref>

== Sphingolipid metabolism ==
{{Main|sphingolipid}}
[[Sphingolipid]]s 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). [[Ceramide]]s 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 [[palmitic acid|palmitoyl]] [[coenzyme A|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.<ref name="pmid16099387">{{cite journal |vauthors=Maceyka M, Milstien S, Spiegel S | title = Sphingosine kinases, sphingosine-1-phosphate and sphingolipidomics | journal = Prostaglandins Other Lipid Mediat. | volume = 77 | issue = 1–4 | pages = 15–22 |date=September 2005 | pmid = 16099387 | doi = 10.1016/j.prostaglandins.2004.09.010 | url = | issn = }}</ref>

[[File:Sphk1 diag b.jpg|thumb|500px|left|De novo synthesis]]
{{Clear}}

== Popular culture ==
During "100,000 Airplanes", a [[The West Wing (season 3)|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 ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite journal |vauthors=Stoffel W, Bauer E, Stahl J | date = 1974 | title = The metabolism of sphingosine bases in Tetrahymena pyriformis Sphingosine kinase and sphingosine-1-phosphate lyase | journal = Hoppe-Seyler's Z. Physiol. Chem.  | volume = 355 | pages = 61&ndash;74  | pmid = 4373374 | issue = 1 | doi = 10.1515/bchm2.1974.355.1.61 }}
* {{cite journal |vauthors=Stoffel W, Heimann G, Hellenbroich B | date = 1973 | title = Sphingosine kinase in blood platelets | journal = Hoppe-Seyler's Z. Physiol. Chem.  | volume = 354 | pages = 562&ndash;6  | pmid = 4372149 | issue = 5 | doi = 10.1515/bchm2.1973.354.1.562 }}
{{refend}}

== External links ==
* {{MeshName|sphingosine+kinase}}

{{Glycolipid/sphingolipid metabolism enzymes}}
{{Lysophospholipid signaling}}
{{Kinases}}
{{Enzymes}}
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{{DEFAULTSORT:Sphingosine Kinase}}
[[Category:EC 2.7.1]]
[[Category:Lipids]]