Hannun and Luberto, Ceramide in the eukaryotic stress response

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Hannun and Luberto, 2000. Ceramide in the eukaryotic stress response Hannun and Luberto, 2000. Ceramide in the eukaryotic stress response. Trends Cell Biol. 10:73-79 Huwlier, et al., 2000.Physiology and pathophysiology of sphingolipid metabolism and signaling. BBA 1485:63-99. Kolesnick, er al., 2000. Comaprtmentalization of ceramide signaling: physical foundations and biological effects. J. Cell Physiol. 184:285. Perry & Hannun, 1998. The role of ceramide in cell signaling . BBA 1436:233. Pyne, S, & Pyne, N. 2000. Sphingosine 1-phosphate signaling in mammalian cells. Biochem. J. 349:385-402. Spiegel & Milstein, 2000. Sphingolipid metabolites in signal transduction. From Signaling networks and cell cycle control, Ed. S. Gutkind, Humana Press, NJ, pp379-391. Spiegel & Milstein. 2000. Sphingosine-1-Phosphate: signaling inside and out FEBS lett. 476:55-57. Oliviera & Spiegel, 2001. Sphingosine kinase: a mediator of vital cellular functions. Prostaglandins Lipid Med. 64:123-134. Venkataraman, K., and Futerman, A.H. 2000. Ceramide as a second messenger:sticky solutions to sticky problems. Trends Cell Biol. 10:408-412,

Sphingolipid Signaling Role of Ceramide and Sphingosine in Cell death Role of Spingosine-1-phosphate in cell survival

Four main types of phospholipids in plasmamembranes

Ceramide has a Sphingosine backbone

Biophysiclal Properties of Ceramide Ceramide, red Sphingolipids, blue Cholesterol, green Ceramide forms natural microdomains: CRD (ceramide rich domains) Venkataraman & Futerman, 2000. Trends Cell Biol. 10:409.

Venkataraman & Futerman, 2000. Trends Cell Biol. 10:411. (a) direct, (b) via ceramide transfer proteins, (c,d) receptor-activation Venkataraman & Futerman, 2000. Trends Cell Biol. 10:411.

Enzymes in Ceramide Metabolism Sphingomyelinase (A and N) Sphingomyelin Synthase Ceramide Kinase Ceramidase Glycosyl Ceramide Synthase Ceramide Synthase

Perry & Hannun, 1998. BBA 1436:234

Huwlier, et al.,2000. BBA 1485:71.

Sphingolipid Metabolism Pyne & Pyne, 2000. Biochem J. 349:386.

Huwlier, et al.,2000. BBA 1485:72.

De novo Ceramide Synthesis Pyne & Pyne, 2000. Biochem J. 349:386.

Ceramide Effects 1. Growth arrest 2. Apoptosis 3. Proliferation 4. Differentiation Perry & Hannun, 1998. BBA 1436:235

Ceramide effectors 1. CAPP: ceramide activated protein phosphatase (PP2A) 2 PP1: protein phosphatase 1 3. CAP kinase: ceramide-activated protein kinase 4. Protein kinase C x 5. C-Raf1

Ceramide Siganling in Apoptosis

Ceramide activation by TNF a Hannun and Luberto, 2000. Trends Cell Biol. 10:77

Sphingolipids in Multidrug Resistance Siestma, et al., 2001. J. Memb. Biol. 181:153

Ceramide Metabolism Hannun & Luberto, 2000 trends Cell Biol. 10:78.

Sphingosine-1-PO4 Signaling

S1P mediated signal cascades

Possible Intracellular Actions of S1P Pyne & Pyne, 2000. Biochem.J. 349:394

Model for Signal termination at EDGRs Pyne & Pyne, 2000. Biochem.J. 349:385-402.

Regulation of Cell Fate by Sphingolipids Pyne & Pyne, 2000. Biochem.J. 349:396