Entry Name Sphingolipid signaling pathway - Monodelphis domestica (gray short-tailed opossum)
Description Sphingomyelin (SM) and its metabolic products are now known to have second messenger functions in a variety of cellular signaling pathways. Particularly, the sphingolipid metabolites, ceramide (Cer) and sphingosine-1-phosphate (S1P), have emerged as a new class of potent bioactive molecules. Ceramide can be generated de novo or by hydrolysis of membrane sphingomyelin by sphingomyelinase (SMase). Ceramide is subsequently metabolized by ceramidase to generate sphingosine (Sph) which in turn produces S1P through phosphorylation by sphingosine kinases 1 and 2 (SphK1, 2). Both ceramide and S1P regulate cellular responses to stress, with generally opposing effects. S1P functions as a growth and survival factor, acting as a ligand for a family of G protein-coupled receptors, whereas ceramide activates intrinsic and extrinsic apoptotic pathways through receptor-independent mechanisms.
Class Environmental Information Processing; Signal transductionBRITE hierarchy
Pathway map Ortholog table Organism Monodelphis domestica (gray short-tailed opossum) [GN:
mdo ]
Gene 100029828 NSMAF; neutral sphingomyelinase activation associated factor [KO:K18953 ]
100026516 PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456 ]
100028805 PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456 ]
100023749 PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354 ]
100014202 PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354 ]
100018121 PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354 ]
100023958 serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354 ]
100011289 PPP2R3B; protein phosphatase 2 regulatory subunit B''beta [KO:K11583 ]
100011688 PPP2R3C; protein phosphatase 2 regulatory subunit B''gamma [KO:K11583 ]
100016573 PPP2R3A; protein phosphatase 2 regulatory subunit B''alpha [KO:K11583 ]
100017824 PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584 ]
100010758 PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584 ]
100022186 PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584 ]
100016488 PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584 ]
103096027 high affinity immunoglobulin epsilon receptor subunit beta-like [KO:K08090 ]
103096457 membrane-spanning 4-domains subfamily A member 5-like [KO:K08090 ]
100019317 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
100032726 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
100616957 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
100027518 SGPP1; sphingosine-1-phosphate phosphatase 1 [KO:K04716 ] [EC:3.1.3.-]
100022862 SGPP2; sphingosine-1-phosphate phosphatase 2 [KO:K04717 ] [EC:3.1.3.-]
554197 NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828 ]
100026992 RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392 ]
100017517 RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860 ]
100029873 RAC3; ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [KO:K07861 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
C06124 Sphingosine 1-phosphate
Reference Authors Hannun YA, Obeid LM
Title Principles of bioactive lipid signalling: lessons from sphingolipids.
Journal Reference Authors Taha TA, Mullen TD, Obeid LM
Title A house divided: ceramide, sphingosine, and sphingosine-1-phosphate in programmed cell death.
Journal Reference Authors Liu J, Beckman BS, Foroozesh M
Title A review of ceramide analogs as potential anticancer agents.
Journal Reference Authors Kono M, Allende ML, Proia RL
Title Sphingosine-1-phosphate regulation of mammalian development.
Journal Reference Authors Olivera A
Title Unraveling the complexities of sphingosine-1-phosphate function: the mast cell model.
Journal Reference Authors Brunkhorst R, Vutukuri R, Pfeilschifter W
Title Fingolimod for the treatment of neurological diseases-state of play and future perspectives.
Journal Reference Authors Rosen H, Goetzl EJ
Title Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network.
Journal Reference Authors Pyne S, Pyne NJ
Title Sphingosine 1-phosphate signalling in mammalian cells.
Journal Reference Authors Egom EE, Mohamed TM, Mamas MA, Shi Y, Liu W, Chirico D, Stringer SE, Ke Y, Shaheen M, Wang T, Chacko S, Wang X, Solaro RJ, Fath-Ordoubadi F, Cartwright EJ, Lei M
Title Activation of Pak1/Akt/eNOS signaling following sphingosine-1-phosphate release as part of a mechanism protecting cardiomyocytes against ischemic cell injury.
Journal Reference Authors Jin ZQ, Goetzl EJ, Karliner JS
Title Sphingosine kinase activation mediates ischemic preconditioning in murine heart.
Journal Reference Authors Melendez AJ
Title Sphingosine kinase signalling in immune cells: potential as novel therapeutic targets.
Journal Reference Authors Halova I, Draberova L, Draber P
Title Mast cell chemotaxis - chemoattractants and signaling pathways.
Journal Reference Authors Kraft S, Kinet JP
Title New developments in FcepsilonRI regulation, function and inhibition.
Journal Reference Authors Gilfillan AM, Tkaczyk C.
Title Integrated signalling pathways for mast-cell activation.
Journal Reference Authors Osawa Y, Banno Y, Nagaki M, Brenner DA, Naiki T, Nozawa Y, Nakashima S, Moriwaki H
Title TNF-alpha-induced sphingosine 1-phosphate inhibits apoptosis through a phosphatidylinositol 3-kinase/Akt pathway in human hepatocytes.
Journal Reference Authors Montfort A, Martin PG, Levade T, Benoist H, Segui B
Title FAN (factor associated with neutral sphingomyelinase activation), a moonlighting protein in TNF-R1 signaling.
Journal Reference Authors Chatterjee S
Title Neutral sphingomyelinase: past, present and future.
Journal Related KO pathway LinkDB All DBs
