Ceramide 1‑Phosphate in Cell Survival and Inflammatory Signaling

Chapter Details

Pub Date: 19 Jul 2010
Pages: 13
Chapter Category: Adhesion Molecules
Taken from the Book: Sphingolipids as Signaling and Regulatory Molecules
Book Series: Special Books
Edited by: Charles Chalfant and Maurizio Del Poeta

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Ceramide 1‑Phosphate in Cell Survival and Inflammatory Signaling

Antonio Gómez-Muñoz, Patricia Gangoiti, María H. Granado, Lide Arana and Alberto Ouro

About this Chapter

An important metabolite of ceramide is ceramide 1‑phosphate (C1P). This lipid second messenger was first demonstrated to be mitogenic for fibroblasts and macrophages and later shown to have antiapoptotic properties. C1P is also an important mediator of the inflammatory response, by stimulating the release of arachidonic acid through activation of group IVA cytosolic phospholipase A2, the initial rate‑limiting step of eicosanoid biosynthesis. C1P is formed from ceramide by the action of a specific ceramide kinase (CerK), which is distinct from the sphingosine kinases that synthesize sphingosine‑1‑phosphate. CerK is specific for natural ceramides with the erythro configuration in the base component and esterified to long‑chain fatty acids. CerK can be activated by different agonists, including interleukin 1‑beta, macrophage colony stimulating factor, or calcium ions. Most of the effects of C1P so far described seem to take place in intracellular compartments; however, the recent observation that C1P stimulates cell migration implicates a specific plasma membrane receptor that is coupled to a Gi protein. Therefore, C1P has a dual regulatory capacity acting as an intracellular second messenger to regulate cell survival, or as extracellular receptor ligand to stimulate chemotaxis.

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