Sphingosine kinase

protein
Name= sphingosine kinase 1
caption=


width=
HGNCid=11240
Symbol=SPHK1
AltSymbols=
EntrezGene=8877
OMIM=603730
RefSeq=NM_182965
UniProt=Q9NYA1
PDB=
ECnumber=
Chromosome=17
Arm=q
Band=25.2
LocusSupplementaryData=protein
Name=sphingosine kinase 2
caption=


width=
HGNCid=18859
Symbol=SPHK2
AltSymbols=
EntrezGene=56848
OMIM=607092
RefSeq=NM_020126
UniProt=Q9NRA0
PDB=
ECnumber=
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 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.

S1P has been shown to regulate diverse cellular processes. Sphingosine 1-phosphate (S1P) 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 (see Refs. [3–6] for recent reviews), 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. [Billich et al., Cellular Signalling 17 (2005) 1203–1217]

phingolipid Metabolism

Sphingolipids are ubiquitous membrane constituents of all eukaryotic cells. The termsphingolipid (SL) generally refers to any of a number of lipids consisting of a head groupattached to the 1-OH of ceramide (Cer). Ceramides consist of a sphingoid base, commonlyreferred to as a long chain base (LCB), which is N-acylated. De novo synthesis of LCBsbegins 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 14–26 carbon fatty acid chain is thenadded 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 the1-OH, forming a sphingolipid, although most sphingolipids of higher eukaryotes contain further modificationsof the LCB. [Spiegel et al., Prostaglandins & other Lipid Mediators 77 (2005) 15–22]

ynthesis

References

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