Sphingosine-dependent apoptosis: A unified concept based on multiple mechanisms operating in concert

Suzuki, Érika; Handa, Kazuko; Toledo, Marcos S.; Hakomori, Sen‐itiroh

doi:10.1073/pnas.0406536101

Cited by 83 publications

(88 citation statements)

References 37 publications

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“…A truncated form of PKC has been described as a sphingosine-dependent protein kinase (SDK1). Substrates of SDK1 include 14-3-3 proteins; phosphorylated 14-3-3 proteins are reported to form dimers, which masks their binding sites and renders them unable to bind to phosphorylated targets 42 . For example, BAD is phosphorylated by PKB/Akt, and is subsequently retained in the cytosol where it is inactivated by 14-3-3 proteins.…”

Section: Box 4 | Nuclear Receptorsmentioning

confidence: 99%

Lipid signalling in disease

Wymann

Schneiter

2008

Nat Rev Mol Cell Biol

1,136

906

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Section: Box 4 | Nuclear Receptorsmentioning

confidence: 99%

Lipid signalling in disease

Wymann

Schneiter

2008

Nat Rev Mol Cell Biol

1,136

906

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“…An increase in sphingosine has been shown to occur in response to TNF-α [61], serum starvation [62], interleukin-1β [63], bradykinin [64], phorbol ester [17], and Fas ligands [65]. The release of sphingosine is presumed to arise from enhanced degradation of complex sphingolipids, sphingomyelin or ceramide.…”

Section: Iii) An Increase In Free Sphingosinementioning

confidence: 99%

The sphingolipid salvage pathway in ceramide metabolism and signaling

Kitatani

Idkowiak‐Baldys

Hannun

2008

Cellular Signalling

539

457

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Sphingolipids are important components of eukaryotic cells, many of which function as bioactive signaling molecules. Of these, ceramide is a central metabolite and plays key roles in a variety of cellular responses, including regulation of cell growth, viability, differentiation, and senescence. Ceramide is composed of the long-chain sphingoid base, sphingosine, in N-linkage to a variety of acyl groups. Sphingosine serves as the product of sphingolipid catabolism, and it is mostly salvaged through re-acylation, resulting in the generation of ceramide or its derivatives. This recycling of sphingosine is termed the "salvage pathway", and recent evidence points to important roles for this pathway in ceramide metabolism and function. A number of enzymes are involved in the salvage pathway, and these include sphingomyelinases, cerebrosidases, ceramidases, and ceramide synthases. Recent studies suggest that the salvage pathway is not only subject to regulation, but it also modulates the formation of ceramide and subsequent ceramide-dependent cellular signals. This review focuses on the salvage pathway in ceramide metabolism, its regulation, its experimental analysis, and emerging biological functions.

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“…In contrast, sphingosine-1-phosphate (S1P) has been mainly characterized as an antiapoptotic lipid, mediating cell proliferation and survival (Cuvillier et al, 1996;Olivera et al, 1999;Paris et al, 2002b). The role of sphingosine in cell death regulation, however, is less clear and has been described both as a proapoptotic (Suzuki et al, 2004) or antiapoptotic (Monick et al, 2004) intermediate. Thus, the relative balance in the generation of pro-vs antiapoptotic sphingolipids may determine the fate of cells in response to cell death stimuli.…”

Section: Introductionmentioning

confidence: 99%