Sphingolipids are a class of lipids containing a backbone of sphingoid bases, which are a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sphinx because of their enigmatic nature. These compounds play important roles in signal transduction and cell recognition. Sphingolipidoses, or disorders of sphingolipid metabolism, have particular impact on neural tissue. A sphingolipid with a terminal hydroxyl group is a ceramide. Other common groups bonded to the terminal oxygen atom include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids.
Lipid signaling, broadly defined, refers to any biological cell signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses. Lipid signaling is thought to be qualitatively different from other classical signaling paradigms because lipids can freely diffuse through membranes. One consequence of this is that lipid messengers cannot be stored in vesicles prior to release and so are often biosynthesized "on demand" at their intended site of action. As such, many lipid signaling molecules cannot circulate freely in solution but, rather, exist bound to special carrier proteins in serum.
Sphingosine-1-phosphate (S1P) is a signaling sphingolipid, also known as lysosphingolipid. It is also referred to as a bioactive lipid mediator. Sphingolipids at large form a class of lipids characterized by a particular aliphatic aminoalcohol, which is sphingosine.
TNF receptor-associated factor 2 is a protein that in humans is encoded by the TRAF2 gene.
Apoptosis signal-regulating kinase 1 (ASK1) also known as mitogen-activated protein kinase 5 (MAP3K5) is a member of MAP kinase family and as such a part of mitogen-activated protein kinase pathway. It activates c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinases in a Raf-independent fashion in response to an array of stresses such as oxidative stress, endoplasmic reticulum stress and calcium influx. ASK1 has been found to be involved in cancer, diabetes, rheumatoid arthritis, cardiovascular and neurodegenerative diseases.
Serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform is an enzyme that is encoded by the PPP2CA gene.
Phospholipase D2 is an enzyme that in humans is encoded by the PLD2 gene.
TNF receptor-associated factor 5 is a protein that in humans is encoded by the TRAF5 gene.
Sphingosine-1-phosphate receptor 1, also known as endothelial differentiation gene 1 (EDG1) is a protein that in humans is encoded by the S1PR1 gene. S1PR1 is a G-protein-coupled receptor which binds the bioactive signaling molecule sphingosine 1-phosphate (S1P). S1PR1 belongs to a sphingosine-1-phosphate receptor subfamily comprising five members (S1PR1-5). S1PR1 was originally identified as an abundant transcript in endothelial cells and it has an important role in regulating endothelial cell cytoskeletal structure, migration, capillary-like network formation and vascular maturation. In addition, S1PR1 signaling is important in the regulation of lymphocyte maturation, migration and trafficking.
Sphingosine-1-phosphate receptor 2, also known as S1PR2 or S1P2, is a human gene which encodes a G protein-coupled receptor which binds the lipid signaling molecule sphingosine 1-phosphate (S1P).
Sphingosine-1-phosphate receptor 5 also known as S1PR5 is a human gene which encodes a G protein-coupled receptor which binds the lipid signaling molecule sphingosine 1-phosphate (S1P). Hence this receptor is also known as S1P5.
Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is a signal transduction enzyme that in humans is encoded by the autosomal MAP3K1 gene.
Heat shock 70 kDa protein 4 is a protein that in humans is encoded by the HSPA4 gene.
ETS translocation variant 1 is a protein that in humans is encoded by the ETV1 gene.
TRAF family member-associated NF-kappa-B activator is a protein that in humans is encoded by the TANK gene.
cGMP-dependent protein kinase 1, alpha isozyme is an enzyme that in humans is encoded by the PRKG1 gene.
Mitogen-activated protein kinase 15, also known as MAPK15, ERK7, or ERK8, is an enzyme that in humans is encoded by the MAPK15 gene.
Dual specificity protein phosphatase 19 is an enzyme that in humans is encoded by the DUSP19 gene.
Sphingosine kinase 2 is a protein that in humans is encoded by the SPHK2 gene.
Sarah Spiegel is professor and chair of the Department of Biochemistry and Molecular Biology at Virginia Commonwealth University (VCU). In the mid-1990s she discovered the sphingosine-1-phosphate (S1P) molecule, a lipid which has been identified as a signaler for the spread of cancer, inflammation, and cardiovascular disease. Her research continues to focus on S1P.
