Sphingosine kinase 1 is an
enzyme
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...
that in humans is encoded by the ''SPHK1''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
Sphingosine kinase 1
phosphorylates
In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols:
:
This equation can be writt ...
sphingosine
Sphingosine (2-amino-4-trans-octadecene-1,3-diol) is an 18-carbon amino alcohol with an unsaturated hydrocarbon chain, which forms a primary part of sphingolipids, a class of cell membrane lipids that include sphingomyelin, an important phosphol ...
to
sphingosine-1-phosphate (S1P). SK1 is normally a
cytosol
The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
ic protein but is recruited to membranes rich in
phosphatidate
Phosphatidic acids are anionic phospholipids important to cell signaling and direct activation of lipid-gated ion channels. Hydrolysis of phosphatidic acid gives rise to one molecule each of glycerol and phosphoric acid and two molecules of fatty a ...
(PA), a product of
phospholipase D
Phospholipase D (PLD) (EC 3.1.4.4; also known as lipophosphodiesterase II, lecithinase D, choline phosphatase; systematic name: phosphatidylcholine phosphatidohydrolase) is an anesthetic-sensitive and mechanosensitive enzyme of the phospholipa ...
(PLD).
(S1P) is a novel
lipid messenger with both intracellular and extracellular functions. Intracellularly, it regulates
proliferation and survival, and extracellularly, it is a ligand for
EDG1. Various stimuli increase cellular levels of S1P by activation of
sphingosine kinase (SPHK), the enzyme that catalyzes the
phosphorylation
In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols:
:
This equation can be writ ...
of
sphingosine
Sphingosine (2-amino-4-trans-octadecene-1,3-diol) is an 18-carbon amino alcohol with an unsaturated hydrocarbon chain, which forms a primary part of sphingolipids, a class of cell membrane lipids that include sphingomyelin, an important phosphol ...
. Competitive inhibitors of SPHK block formation of S1P and selectively inhibit cellular proliferation induced by a variety of factors, including
platelet-derived growth factor
Platelet-derived growth factor (PDGF) is one among numerous growth factors that regulate cell growth and division. In particular, PDGF plays a significant role in blood vessel formation, the growth of blood vessels from already-existing bloo ...
and serum.
Interactions
SPHK1 has been shown to
interact with
TRAF2
TNF receptor-associated factor 2 is a protein that in humans is encoded by the ''TRAF2'' gene.
Function
The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, a ...
.
References
Further reading
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External links
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EC 2.7.1
{{gene-17-stub