Principles of bioactive lipid signalling: lessons from sphingolipids (original) (raw)
Hokin, M. R. & Hokin, L. E. Enzyme secretion and the incorporation of 32P into phospholipids of pancreas slices. J. Biol. Chem.203, 967–977 (1953). Earliest study to demonstrate agonist-induced turnover of inositol phospholipids. CASPubMed Google Scholar
Nishizuka, Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science258, 607–614 (1992). An excellent review, by a pioneer in the field on bioactive lipids, that discusses the discovery of activation of PKC by DAG. CASPubMed Google Scholar
Serhan, C. N. & Savill, J. Resolution of inflammation: the beginning programs the end. Nature Immunol.6, 1191–1197 (2005). CAS Google Scholar
Smith, E. R., Merrill, A. H., Obeid, L. M. & Hannun, Y. A. Effects of sphingosine and other sphingolipids on protein kinase C. Methods Enzymol.312, 361–373 (2000). CASPubMed Google Scholar
Obeid, L. M., Linardic, C. M., Karolak, L. A. & Hannun, Y. A. Programmed cell death induced by ceramide. Science259, 1769–1771 (1993). A landmark study that implicated ceramide in apoptosis. CASPubMed Google Scholar
Venable, M. E., Lee, J. Y., Smyth, M. J., Bielawska, A. & Obeid, L. M. Role of ceramide in cellular senescence. J. Biol. Chem.270, 30701–30708 (1995). The first study to implicate ceramide in cellular senescence. CASPubMed Google Scholar
Hla, T. Physiological and pathological actions of sphingosine 1-phosphate. Semin. Cell Dev. Biol.15, 513–520 (2004). CASPubMed Google Scholar
Chalfant, C. E. & Spiegel, S. Sphingosine 1-phosphate and ceramide 1-phosphate: expanding roles in cell signaling. J. Cell Sci.118, 4605–4612 (2005). CASPubMed Google Scholar
Mitsutake, S. et al. Ceramide kinase is a mediator of calcium-dependent degranulation in mast cells. J. Biol. Chem.279, 17570–17577 (2004). CASPubMed Google Scholar
Hinkovska-Galcheva, V. et al. Ceramide 1-phosphate, a mediator of phagocytosis. J. Biol. Chem.280, 26612–26621 (2005). CASPubMed Google Scholar
Radin, N. S., Shayman, J.A. & Inokuchi, J.-I. Metabolic effects of inhibiting glucosylceramide synthesis with PDMP and other substances. Adv. Lipid Res.26, 183–211 (1993). CASPubMed Google Scholar
Gouaze-Andersson, V. & Cabot, M. C. Glycosphingolipids and drug resistance. Biochim. Biophys. Acta1758, 2096–2103 (2006). CASPubMed Google Scholar
Hannun, Y. A. & Obeid, L. M. The ceramide-centric universe of lipid-mediated cell regulation: stress encounters of the lipid kind. J. Biol. Chem.277, 25847–25850 (2002). CASPubMed Google Scholar
Linn, S. C. et al. Regulation of de novo sphingolipid biosynthesis and the toxic consequences of its disruption. Biochem. Soc. Trans.29, 831–835 (2001). CASPubMed Google Scholar
Pewzner-Jung, Y., Ben-Dor, S. & Futerman, A. H. When do Lasses (longevity assurance genes) become CerS (ceramide synthases)?: insights into the regulation of ceramide synthesis. J. Biol. Chem.281, 25001–25005 (2006). CASPubMed Google Scholar
Causeret, C., Geeraert, L., Van der Hoeven, G., Mannaerts, G. P. & van Veldhoven, P. P. Further characterization of rat dihydroceramide desaturase: tissue distribution, subcellular localization, and substrate specificity. Lipids35, 1117–1125 (2000). CASPubMed Google Scholar
Wijesinghe, D. S. et al. Substrate specificity of human ceramide kinase. J. Lipid Res.46, 2706–2716 (2005). CASPubMed Google Scholar
Raas-Rothschild, A., Pankova-Kholmyansky, I., Kacher, Y. & Futerman, A. H. Glycosphingolipidoses: beyond the enzymatic defect. Glycoconj. J.21, 295–304 (2004). CASPubMed Google Scholar
Tafesse, F. G., Ternes, P. & Holthuis, J. C. The multigenic sphingomyelin synthase family. J. Biol. Chem.281, 29421–29425 (2006). CASPubMed Google Scholar
Hakomori, S. Traveling for the glycosphingolipid path. Glycoconj. J.17, 627–647 (2000). CASPubMed Google Scholar
Ichikawa, S. & Hirabayashi, Y. Glucosylceramide synthase and glycosphingolipid synthesis. Trends Cell Biol.8, 198–202 (1998). CASPubMed Google Scholar
Marchesini, N. & Hannun, Y. A. Acid and neutral sphingomyelinases: roles and mechanisms of regulation. Biochem. Cell Biol.82, 27–44 (2004). CASPubMed Google Scholar
Xu, R. et al. Golgi alkaline ceramidase regulates cell proliferation and survival by controlling levels of sphingosine and S1P. FASEB J.20, 1813–1825 (2006). CASPubMed Google Scholar
Galadari, S. et al. Identification of a novel amidase motif in neutral ceramidase. Biochem. J.393, 687–695 (2006). CASPubMedPubMed Central Google Scholar
Hait, N. C., Oskeritzian, C. A., Paugh, S. W., Milstien, S. & Spiegel, S. Sphingosine kinases, sphingosine 1-phosphate, apoptosis and diseases. Biochim. Biophys. Acta1758, 2016–2026 (2006). CASPubMed Google Scholar
Johnson, K. R. et al. Role of human sphingosine-1-phosphate phosphatase 1 in the regulation of intra- and extracellular sphingosine-1-phosphate levels and cell viability. J. Biol. Chem.278, 34541–34547 (2003). CASPubMed Google Scholar
Brindley, D. N. Lipid phosphate phosphatases and related proteins: signaling functions in development, cell division, and cancer. J. Cell Biochem.92, 900–912 (2004). CASPubMed Google Scholar
Sigal, Y. J., McDermott, M. I. & Morris, A. J. Integral membrane lipid phosphatases/phosphotransferases: common structure and diverse functions. Biochem. J.387, 281–293 (2005). CASPubMedPubMed Central Google Scholar
Bandhuvula, P. & Saba, J. D. Sphingosine-1-phosphate lyase in immunity and cancer: silencing the siren. Trends Mol. Med.13, 210–217 (2007). CASPubMed Google Scholar
Bielawski, J., Szulc, Z. M., Hannun, Y. A. & Bielawska, A. Simultaneous quantitative analysis of bioactive sphingolipids by high-performance liquid chromatography–tandem mass spectrometry. Methods39, 82–91 (2006). CASPubMed Google Scholar
Merrill, A. H. Jr, Sullards, M. C., Allegood, J. C., Kelly, S. & Wang, E. Sphingolipidomics: high-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry. Methods36, 207–224 (2005). A comprehensive and cutting-edge review on mass spectrometry methodology to analyse the sphingolipidome. CASPubMed Google Scholar
Romiti, E. et al. Characterization of sphingomyelinase activity released by thrombin-stimulated platelets. Mol. Cell. Biochem.205, 75–81 (2000). CASPubMed Google Scholar
Delon, C. et al. Sphingosine kinase 1 is an intracellular effector of phosphatidic acid. J. Biol. Chem.279, 44763–44774 (2004). CASPubMed Google Scholar
Lopez-Montero, I. et al. Rapid transbilayer movement of ceramides in phospholipid vesicles and in human erythrocytes. J. Biol. Chem.280, 25811–25819 (2005). CASPubMed Google Scholar
Khan, W. A. et al. Use of D-erythro-sphingosine as a pharmacologic inhibitor of protein kinase C in human platelets. Biochem. J.278, 387–392 (1991). CASPubMedPubMed Central Google Scholar
Xia, P. et al. Tumor necrosis factor-α induces adhesion molecule expression through the sphingosine kinase pathway. Proc. Natl Acad. Sci. USA95, 14196–14201 (1998). An important study that first demonstrated the activation of sphingosine kinase by TNFα. CASPubMedPubMed Central Google Scholar
Pettus, B. J. et al. The sphingosine kinase 1/sphingosine-1-phosphate pathway mediates COX-2 induction and PGE2 production in response to TNF-α. FASEB J.17, 1411–1421 (2003). An important study that implicates the SK1–S1P pathway in inflammation. CASPubMed Google Scholar
Hla, T., Lee, M. J., Ancellin, N., Paik, J. H. & Kluk, M. J. Lysophospholipids — receptor revelations. Science294, 1875–1878 (2001). CASPubMed Google Scholar
Boujaoude, L. C. et al. Cystic fibrosis transmembrane regulator regulates uptake of sphingoid base phosphates and lysophosphatidic acid: modulation of cellular activity of sphingosine 1-phosphate. J. Biol. Chem.276, 35258–35264 (2001). CASPubMed Google Scholar
Mitra, P. et al. Role of ABCC1 in export of sphingosine-1-phosphate from mast cells. Proc. Natl Acad. Sci. USA103, 16394–16399 (2006). CASPubMedPubMed Central Google Scholar
Hanada, K. et al. Molecular machinery for non-vesicular trafficking of ceramide. Nature426, 803–809 (2003). A breakthrough study on the discovery of ceramide transfer protein. CASPubMed Google Scholar
Fugmann, T. et al. Regulation of secretory transport by protein kinase D-mediated phosphorylation of the ceramide transfer protein. J. Cell Biol.178, 15–22 (2007). CASPubMedPubMed Central Google Scholar
Chalfant, C. E., Szulc, Z., Roddy, P., Bielawska, A. & Hannun, Y. A. The structural requirements for ceramide activation of serine–threonine protein phosphatases. J. Lipid Res.45, 496–506 (2004). CASPubMed Google Scholar
Dbaibo, G. et al. Rb as a downstream target for a ceramide-dependent pathway of growth arrest. Proc. Natl Acad. Sci. USA92, 1347–1351 (1995). CASPubMedPubMed Central Google Scholar
Lee, J. Y., Hannun, Y. A. & Obeid, L. M. Ceramide inactivates cellular protein kinase Cα. J. Biol. Chem.271, 13169–13174 (1996). CASPubMed Google Scholar
Zhou, H. L., Summers, S. K., Birnbaum, M. J. & Pittman, R. N. Inhibition of Akt kinase by cell-permeable ceramide and its implications for ceramide-induced apoptosis. J. Biol. Chem.273, 16568–16575 (1998). CASPubMed Google Scholar
Müller, G. et al. PKCζ is a molecular switch in signal transduction of TNF-α, bifunctionally regulated by ceramide and arachidonic acid. EMBO J.14, 1961–1969 (1995). PubMedPubMed Central Google Scholar
Bourbon, N. A., Sandirasegarane, L. & Kester, M. Ceramide-induced inhibition of Akt is mediated through protein kinase Cζ: implications for growth arrest. J. Biol. Chem.277, 3286–3292 (2002). CASPubMed Google Scholar
Zhang, Y. H. et al. Kinase suppressor of Ras is ceramide-activated protein kinase. Cell89, 63–72 (1997). CASPubMed Google Scholar
Heinrich, M. et al. Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation. Cell Death Differ.11, 550–563 (2004). CASPubMed Google Scholar
Wang, G. et al. Direct binding to ceramide activates protein kinase Cζ before the formation of a pro-apoptotic complex with PAR-4 in differentiating stem cells. J. Biol. Chem.280, 26415–26424 (2005). CASPubMed Google Scholar
Okajima, F. Plasma lipoproteins behave as carriers of extracellular sphingosine 1-phosphate: is this an atherogenic mediator or an anti-atherogenic mediator? Biochim. Biophys. Acta1582, 132–137 (2002). CASPubMed Google Scholar
Lee, M. J. et al. Sphingosine-1-phosphate as a ligand for the G protein coupled receptor EDG-1. Science279, 1552–1555 (1998). The first study to identify and characterize an S1P receptor. CASPubMed Google Scholar
Bose, R. et al. Ceramide synthase mediates daunorubicin-induced apoptosis: an alternative mechanism for generating death signals. Cell82, 405–414 (1995). An important study implicating ceramide synthase in chemotherapy-induced apoptosis. CASPubMed Google Scholar
Perry, D. K. et al. Serine palmitoyltransferase regulates de novo ceramide generation during etoposide-induced apoptosis. J. Biol. Chem.275, 9078–9084 (2000). CASPubMed Google Scholar
Kroesen, B. J. et al. BcR-induced apoptosis involves differential regulation of C16 and C24-ceramide formation and sphingolipid-dependent activation of the proteasome. J. Biol. Chem.278, 14723–14731 (2003). CASPubMed Google Scholar
Chalfant, C. E. et al. De novo ceramide regulates the alternative splicing of caspase 9 and Bcl-x in A549 lung adenocarcinoma cells. Dependence on protein phosphatase-1. J. Biol. Chem.277, 12587–12595 (2002). CASPubMed Google Scholar
Merrill, A. H. Jr, Wang, E. & Mullins, R. E. Kinetics of long-chain (sphingoid) base biosynthesis in intact LM cells: effects of varying the extracellular concentrations of serine and fatty acid precursors of this pathway. Biochemistry27, 340–345 (1988). CASPubMed Google Scholar
Cowart, L. A. & Hannun, Y. A. Selective substrate supply in the regulation of yeast de novo sphingolipid synthesis. J. Biol. Chem.282, 12330–12340 (2007). CASPubMed Google Scholar
Dickson, R. C., Sumanasekera, C. & Lester, R. L. Functions and metabolism of sphingolipids in Saccharomyces cerevisiae. Prog. Lipid Res.45, 447–465 (2006). CASPubMed Google Scholar
Chung, N., Mao, C., Heitman, J., Hannun, Y. A. & Obeid, L. M. Phytosphingosine as a specific inhibitor of growth and nutrient import in Saccharomyces cerevisiae. J. Biol. Chem.276, 35614–35621 (2001). CASPubMed Google Scholar
Friant, S., Lombardi, R., Schmelzle, T., Hall, M. N. & Riezman, H. Sphingoid base signaling via Pkh kinases is required for endocytosis in yeast. EMBO J.20, 6783–6792 (2001). CASPubMedPubMed Central Google Scholar
Meier, K. D., Deloche, O., Kajiwara, K., Funato, K. & Riezman, H. Sphingoid base is required for translation initiation during heat stress in Saccharomyces cerevisiae. Mol. Biol. Cell17, 1164–1175 (2006). CASPubMedPubMed Central Google Scholar
Unger, R. H. Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology144, 5159–5165 (2003). CASPubMed Google Scholar
Holland, W. L. et al. Inhibition of ceramide synthesis ameliorates glucocorticoid-, saturated-fat-, and obesity-induced insulin resistance. Cell Metab.5, 167–179 (2007). An important study that implicates ceramide in insulin resistance. CASPubMed Google Scholar
Rotolo, J. A. et al. Caspase-dependent and -independent activation of acid sphingomyelinase signaling. J. Biol. Chem.280, 26425–26434 (2005). CASPubMed Google Scholar
Lozano, J. et al. Cell autonomous apoptosis defects in acid sphingomyelinase knockout fibroblasts. J. Biol. Chem.276, 442–448 (2001). CASPubMed Google Scholar
Garcia-Barros, M. et al. Tumor response to radiotherapy regulated by endothelial cell apoptosis. Science300, 1155–1159 (2003). CASPubMed Google Scholar
Zeidan, Y. H., Wu, B. X., Jenkins, R. W., Obeid, L. M. & Hannun, Y. A. A novel role for protein kinase Cδ-mediated phosphorylation of acid sphingomyelinase in UV light-induced mitochondrial injury. FASEB J. 13 Aug 2007 (doi:10.1096/fj.07-8967com). CASPubMed Google Scholar
Grassme, H., Riehle, A., Wilker, B. & Gulbins, E. Rhinoviruses infect human epithelial cells via ceramide-enriched membrane platforms. J. Biol. Chem.280, 26256–26262 (2005). CASPubMed Google Scholar
Zeidan, Y. H. et al. Acid ceramidase but not acid sphingomyelinase is required for tumor necrosis factor-α-induced PGE2 production. J. Biol. Chem.281, 24695–24703 (2006). CASPubMed Google Scholar
Zeidan, Y. H. & Hannun, Y. A. Activation of acid sphingomyelinase by protein kinase Cδ-mediated phosphorylation. J. Biol. Chem.282, 11549–11561 (2007). CASPubMed Google Scholar
Lin, T. et al. Role of acidic sphingomyelinase in Fas/CD95-mediated cell death. J. Biol. Chem.275, 8657–8663 (2000). CASPubMed Google Scholar
Nix, M. & Stoffel, W. Perturbation of membrane microdomains reduces mitogenic signaling and increases susceptibility to apoptosis after T cell receptor stimulation. Cell Death Differ.7, 413–424 (2000). CASPubMed Google Scholar
Castillo, S. S., Levy, M., Thaikoottathil, J. V. & Goldkorn, T. Reactive nitrogen and oxygen species activate different sphingomyelinases to induce apoptosis in airway epithelial cells. Exp. Cell Res.313, 2680–2686 (2007). CASPubMed Google Scholar
Becker, K. P., Kitatani, K., Idkowiak-Baldys, J., Bielawski, J. & Hannun, Y. A. Selective inhibition of juxtanuclear translocation of protein kinase C βII by a negative feedback mechanism involving ceramide formed from the salvage pathway. J. Biol. Chem.280, 2606–2612 (2005). CASPubMed Google Scholar
Clarke, C. J. et al. The extended family of neutral sphingomyelinases. Biochemistry45, 11247–11256 (2006). CASPubMed Google Scholar
Hofmann, K., Tomiuk, S., Wolff, G. & Stoffel, W. Cloning and characterization of the mammalian brain-specific, Mg2+-dependent neutral sphingomyelinase. Proc. Natl Acad. Sci. USA97, 5895–5900 (2000). CASPubMedPubMed Central Google Scholar
Marchesini, N., Luberto, C. & Hannun, Y. A. Biochemical properties of mammalian neutral sphingomyelinase 2 and its role in sphingolipid metabolism. J. Biol. Chem.278, 13775–13783 (2003). CASPubMed Google Scholar
Aubin, I. et al. A deletion in the gene encoding sphingomyelin phosphodiesterase 3 (Smpd3) results in osteogenesis and dentinogenesis imperfecta in the mouse. Nature Genet.37, 803–805 (2005). CASPubMed Google Scholar
Stoffel, W. et al. Neutral sphingomyelinase (SMPD3) deficiency causes a novel form of chondrodysplasia and dwarfism that is rescued by Col2A1-driven smpd3 transgene expression. Am. J. Pathol.171, 153–161 (2007). CASPubMedPubMed Central Google Scholar
Karakashian, A. A., Giltiay, N. V., Smith, G. M. & Nikolova-Karakashian, M. N. Expression of neutral sphingomyelinase-2 (NSMase-2) in primary rat hepatocytes modulates IL-β-induced JNK activation. FASEB J.18, 968–970 (2004). CASPubMed Google Scholar
De Palma, C., Meacci, E., Perrotta, C., Bruni, P. & Clementi, E. Endothelial nitric oxide synthase activation by tumor necrosis factor α through neutral sphingomyelinase 2, sphingosine kinase 1, and sphingosine 1 phosphate receptors: a novel pathway relevant to the pathophysiology of endothelium. Arterioscler. Thromb. Vasc. Biol.26, 99–105 (2006). CASPubMed Google Scholar
Rutkute, K., Karakashian, A. A., Giltiay, N. V., Dobierzewska, A. & Nikolova-Karakashian, M. N. Aging in rat causes hepatic hyperresponsiveness to interleukin-1β which is mediated by neutral sphingomyelinase-2. Hepatology46, 1166–1176 (2007). A crucial study that demonstrates a role for ceramide and sphingomyelin in ageingin vivo. CASPubMed Google Scholar
Clarke, C. J., Truong, T. G. & Hannun, Y. A. Role for neutral sphingomyelinase-2 in tumor necrosis factor α-stimulated expression of vascular cell adhesion molecule-1 (VCAM) and intercellular adhesion molecule-1 (ICAM) in lung epithelial cells: p38 MAPK is an upstream regulator of nSMase2. J. Biol. Chem.282, 1384–1396 (2007). CASPubMed Google Scholar
Grimm, M. O. et al. Regulation of cholesterol and sphingomyelin metabolism by amyloid-β and presenilin. Nature Cell Biol.7, 1118–1123 (2005). CASPubMed Google Scholar
Zeng, C. et al. Amyloid-β peptide enhances tumor necrosis factor-α-induced iNOS through neutral sphingomyelinase/ceramide pathway in oligodendrocytes. J. Neurochem.94, 703–712 (2005). CASPubMed Google Scholar
Hayashi, Y., Kiyono, T., Fujita, M. & Ishibashi, M. cca1 is required for formation of growth-arrested confluent monolayer of rat 3Y1 cells. J. Biol. Chem.272, 18082–18086 (1997). CASPubMed Google Scholar
Marchesini, N. et al. Role for mammalian neutral sphingomyelinase 2 in confluence-induced growth arrest of MCF7 cells. J. Biol. Chem.279, 25101–25111 (2004). CASPubMed Google Scholar
Tani, M. & Hannun, Y. A. Analysis of membrane topology of neutral sphingomyelinase 2. FEBS Lett.581, 1323–1328 (2007). CASPubMedPubMed Central Google Scholar
Spiegel, S. & Milstien, S. Sphingosine-1-phosphate: an enigmatic signalling lipid. Nature Rev. Mol. Cell Biol.4, 397–407 (2003). CAS Google Scholar
Johnson, K. R., Becker, K. P., Facchinetti, M. M., Hannun, Y. A. & Obeid, L. M. PKC-dependent activation of sphingosine kinase 1 and translocation to the plasma membrane. Extracellular release of sphingosine-1-phosphate induced by phorbol 12-myristate 13-acetate (PMA). J. Biol. Chem.277, 35257–35262 (2002). CASPubMed Google Scholar
Melendez, A., Floto, R. A., Gillooly, D. J., Harnett, M. M. & Allen, J. M. FcγRI coupling to phospholipase D initiates sphingosine kinase-mediated calcium mobilization and vesicular trafficking. J. Biol. Chem.273, 9393–9402 (1998). CASPubMed Google Scholar
Pitson, S. M. et al. Activation of sphingosine kinase 1 by ERK1/2-mediated phosphorylation. EMBO J.22, 5491–5500 (2003). CASPubMedPubMed Central Google Scholar
Taha, T. A., Argraves, K. M. & Obeid, L. M. Sphingosine-1-phosphate receptors: receptor specificity versus functional redundancy. Biochim. Biophys. Acta1682, 48–55 (2004). CASPubMed Google Scholar
Xia, P. et al. Sphingosine kinase interacts with TRAF2 and dissects tumor necrosis factor-α signaling. J. Biol. Chem.277, 7996–8003 (2002). CASPubMed Google Scholar
Billich, A. et al. Basal and induced sphingosine kinase 1 activity in A549 carcinoma cells: function in cell survival and IL-1β and TNF-α induced production of inflammatory mediators. Cell Signal.17, 1203–1217 (2005). CASPubMed Google Scholar
Lee, M. J. et al. Vascular endothelial cell adherens junction assembly and morphogenesis induced by sphingosine-1-phosphate. Cell99, 301–312 (1999). CASPubMed Google Scholar
Liu, Y. et al. Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation. J. Clin. Invest.106, 951–961 (2000). CASPubMedPubMed Central Google Scholar
Mizugishi, K. et al. Essential role for sphingosine kinases in neural and vascular development. Mol. Cell. Biol.25, 11113–11121 (2005). CASPubMedPubMed Central Google Scholar
Peters, S. L. & Alewijnse, A. E. Sphingosine-1-phosphate signaling in the cardiovascular system. Curr. Opin. Pharmacol.7, 186–192 (2007). CASPubMed Google Scholar
Rosen, H., Sanna, G. & Alfonso, C. Egress: a receptor-regulated step in lymphocyte trafficking. Immunol. Rev.195, 160–177 (2003). CASPubMed Google Scholar
Gonsette, R. E. New immunosuppressants with potential implication in multiple sclerosis. J. Neurol. Sci.223, 87–93 (2004). CASPubMed Google Scholar
Taha, T. A. et al. Loss of sphingosine kinase-1 activates the intrinsic pathway of programmed cell death: modulation of sphingolipid levels and the induction of apoptosis. FASEB J.20, 482–484 (2006). CASPubMed Google Scholar
Pettus, B. J. et al. Ceramide 1-phosphate is a direct activator of cytosolic phospholipase A2. J. Biol. Chem.279, 11320–11326 (2004). CASPubMed Google Scholar
Mitsutake, S. & Igarashi, Y. Calmodulin is involved in the Ca2+-dependent activation of ceramide kinase as a calcium sensor. J. Biol. Chem.280, 40436–40441 (2005). CASPubMed Google Scholar
Gomez-Munoz, A. Ceramide 1-phosphate/ceramide, a switch between life and death. Biochim. Biophys. Acta1758, 2049–2056 (2006). CASPubMed Google Scholar
Raggers, R. J., van Helvoort, A., Evers, R. & van Meer, G. The human multidrug resistance protein MRP1 translocates sphingolipid analogs across the plasma membrane. J. Cell Sci.112, 415–422 (1999). CASPubMed Google Scholar
Schulz, A. et al. The CLN9 protein, a regulator of dihydroceramide synthase. J. Biol. Chem.281, 2784–2794 (2006). CASPubMed Google Scholar
Kraveka, J. M. et al. Involvement of dihydroceramide desaturase in cell cycle progression in human neuroblastoma cells. J. Biol. Chem.282, 16718–16728 (2007). CASPubMed Google Scholar
Zheng, W. et al. Ceramides and other bioactive sphingolipid backbones in health and disease: lipidomic analysis, metabolism and roles in membrane structure, dynamics, signaling and autophagy. Biochim. Biophys. Acta1758, 1864–1884 (2006). CASPubMed Google Scholar
Ignatov, A. et al. Role of the G-protein-coupled receptor GPR12 as high-affinity receptor for sphingosylphosphorylcholine and its expression and function in brain development. J. Neurosci.23, 907–914 (2003). CASPubMedPubMed Central Google Scholar
Zeidan, Y. H. & Hannun, Y. A. Translational aspects of sphingolipid metabolism. Trends Mol. Med.13, 327–336 (2007). CASPubMed Google Scholar
Radin, N. S. Designing anticancer drugs via the achilles heel: ceramide, allylic ketones, and mitochondria. Bioorg. Med. Chem.11, 2123–2142 (2003). CASPubMed Google Scholar
Summers, S. A. Ceramides in insulin resistance and lipotoxicity. Prog. Lipid Res.45, 42–72 (2006). CASPubMed Google Scholar
Wattenberg, B. W., Pitson, S. M. & Raben, D. M. The sphingosine and diacylglycerol kinase superfamily of signaling kinases: localization as a key to signaling function. J. Lipid Res.47, 1128–1139 (2006). CASPubMed Google Scholar
Alvarez-Vasquez, F. et al. Simulation and validation of modelled sphingolipid metabolism in Saccharomyces cerevisiae. Nature433, 425–430 (2005). CASPubMed Google Scholar
D'Angelo, G. et al. Glycosphingolipid synthesis requires FAPP2 transfer of glucosylceramide. Nature449, 62–67 (2007). CASPubMed Google Scholar