The role of sphingosine and ceramide kinases in inflammatory responses.
The 1-phosphates of sphingosine and ceramide (S1P and C1P) have emerged as key representatives of a new group of lipid signalling molecules. S1P is known to act both as an extracellular mediator and as an intracellular 'second messenger,' while C1P currently is only known for its intracellular actions. Therefore, sphingosine and ceramide kinases, the enzymes involved in the generation of these lipid mediators, are now in the spotlight. This review summarizes current information on structure, localization, substrate specificity, activation, and binding partners of these kinases, and then focuses on discoveries in relation to immune cell regulation and inflammation, addressing in particular mast cell activation and degranulation, IL-12 signalling, prostaglandin biosynthesis, monocyte activation, and neutrophil priming.
Baumruker
Thomas
T
Novartis Institute for BioMedical Research Vienna, Brunner Strasse 59, A-1235 Vienna, Austria. thomas.baumruker@pharma.novartis.com
Bornancin
Frédéric
F
Billich
Andreas
A
D000818:Animals; D002518:Ceramides / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D007249:Inflammation / Q000201:enzymology* / Q000378:metabolism; D008264:Macrophages / Q000502:physiology; D008407:Mast Cells / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D011487:Protein Conformation; D015398:Signal Transduction; D013110:Sphingosine / Q000378:metabolism; D013379:Substrate Specificity; D000099157:Sphingosine Kinase
D002518:Ceramides; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D000099157:Sphingosine Kinase; C066324:ceramide kinase