Entry Name Sphingolipid signaling pathway
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 ko04071 Sphingolipid signaling pathway
Ortholog table Orthology K26384 serine palmitoyltransferase small subunit
K03156 tumor necrosis factor superfamily, member 2
K03158 tumor necrosis factor receptor superfamily member 1A
K18953 factor associated with neutral sphingomyelinase activation
K03171 tumor necrosis factor receptor type 1-associated DEATH domain protein
K04726 BH3 interacting domain death agonist
K02159 apoptosis regulator BAX
K04440 mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24 ]
K02161 apoptosis regulator Bcl-2
K04382 serine/threonine-protein phosphatase 2A catalytic subunit [EC:3.1.3.16 ]
K03456 serine/threonine-protein phosphatase 2A regulatory subunit A
K04354 serine/threonine-protein phosphatase 2A regulatory subunit B
K11583 serine/threonine-protein phosphatase 2A regulatory subunit B''
K11584 serine/threonine-protein phosphatase 2A regulatory subunit B'
K08089 high affinity immunoglobulin epsilon receptor subunit alpha
K08090 high affinity immunoglobulin epsilon receptor subunit beta
K07983 high affinity immunoglobulin epsilon receptor subunit gamma
K08091 GRB2-associated-binding protein 2
K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02649 phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K04213 delta-type opioid receptor
K04630 guanine nucleotide-binding protein G(i) subunit alpha
K04716 sphingosine-1-phosphate phosphatase 1 [EC:3.1.3.-]
K04717 sphingosine-1-phosphate phosphotase 2 [EC:3.1.3.-]
K05665 ATP-binding cassette, subfamily C (CFTR/MRP), member 1 [EC:7.6.2.3 ]
K04288 sphingosine 1-phosphate receptor 1
K04292 sphingosine 1-phosphate receptor 2
K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04392 Ras-related C3 botulinum toxin substrate 1
K07860 Ras-related C3 botulinum toxin substrate 2
K07861 Ras-related C3 botulinum toxin substrate 3
K04290 sphingosine 1-phosphate receptor 3
K04634 guanine nucleotide-binding protein G(q) subunit alpha
K04293 sphingosine 1-phosphate receptor 4
K04295 sphingosine 1-phosphate receptor 5
K04346 guanine nucleotide-binding protein subunit alpha-12
K04639 guanine nucleotide-binding protein subunit alpha-13
K04513 Ras homolog gene family, member A
K02580 nuclear factor NF-kappa-B p105 subunit
K04735 transcription factor p65
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 LinkDB All DBs
