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Ceramide 1-phosphate/ceramide, a switch between life and death
Authors:Antonio Gómez-Muñoz
Institution:Department of Biochemistry and Molecular Biology. Faculty of Science and Technology. University of the Basque Country. P.O. Box 644. 48080-Bilbao, Spain
Abstract:Ceramide is a well-characterized sphingolipid metabolite and second messenger that participates in numerous biological processes. In addition to serving as a precursor to complex sphingolipids, ceramide is a potent signaling molecule capable of regulating vital cellular functions. Perhaps its major role in signal transduction is to induce cell cycle arrest, and promote apoptosis. In contrast, little is known about the metabolic or signaling pathways that are regulated by the phosphorylated form of ceramide. It was first demonstrated that ceramide-1-phosphate (C1P) had mitogenic properties, and more recently it has been described as potent inhibitor of apoptosis and inducer of cell survival. C1P and ceramide are antagonistic molecules that can be interconverted in cells by kinase and phosphatase activities. An appropriate balance between the levels of these two metabolites seems to be crucial for cell and tissue homeostasis. Switching this balance towards accumulation of one or the other may result in metabolic dysfunction, or disease. Therefore, the activity of the enzymes that are involved in C1P and ceramide metabolism must be efficiently coordinated to ensure normal cell functioning.
Keywords:C2-ceramide  N-acetylsphingosine  C8-ceramide  N-octanoylsphingosine  CERK  ceramide kinase  C1P  ceramide-1-phosphate  DAG  diacylglycerol  ERK  extracellular regulated kinase  MAPK  mitogen-activated protein kinase  M-CSF  monocyte-colony stimulating factor  PA  phosphatidate  PI3-K  phosphatidylinositol 3-kinase  PKA  cAMP-dependent protein kinase  PKB  protein kinase B  PLA2  phospholipase A2  PKC  protein kinase C  PLD  phospholipase D  SM  sphingomyelin  SMase  sphingomyelinase  S1P  sphingosine-1-phosphate
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