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Hannun and Luberto, Ceramide in the eukaryotic stress response

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Presentation on theme: "Hannun and Luberto, Ceramide in the eukaryotic stress response"— Presentation transcript:

1 Hannun and Luberto, 2000. Ceramide in the eukaryotic stress response
Hannun and Luberto, 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., Comaprtmentalization of ceramide signaling: physical foundations and biological effects. J. Cell Physiol. 184:285. Perry & Hannun, The role of ceramide in cell signaling . BBA 1436:233. Pyne, S, & Pyne, N Sphingosine 1-phosphate signaling in mammalian cells. Biochem. J. 349: Spiegel & Milstein, Sphingolipid metabolites in signal transduction. From Signaling networks and cell cycle control, Ed. S. Gutkind, Humana Press, NJ, pp Spiegel & Milstein Sphingosine-1-Phosphate: signaling inside and out FEBS lett. 476:55-57. Oliviera & Spiegel, Sphingosine kinase: a mediator of vital cellular functions. Prostaglandins Lipid Med. 64: Venkataraman, K., and Futerman, A.H Ceramide as a second messenger:sticky solutions to sticky problems. Trends Cell Biol. 10: ,

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

3 Four main types of phospholipids in plasmamembranes

4

5 Ceramide has a Sphingosine backbone

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

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

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

9 Perry & Hannun, BBA 1436:234

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

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

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

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

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

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

16 Ceramide Siganling in Apoptosis

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

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

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

20 Sphingosine-1-PO4 Signaling

21 S1P mediated signal cascades

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

23 Model for Signal termination at EDGRs
Pyne & Pyne, Biochem.J. 349:

24

25

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

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