KEGG   PATHWAY: etf04071
Entry
etf04071                    Pathway                                
Name
Sphingolipid signaling pathway - Echinops telfairi (small Madagascar hedgehog)
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 transduction
Pathway map
etf04071  Sphingolipid signaling pathway
etf04071

Organism
Echinops telfairi (small Madagascar hedgehog) [GN:etf]
Gene
101643664  SPTLC3; serine palmitoyltransferase 3 [KO:K00654] [EC:2.3.1.50]
101652877  SPTLC1; serine palmitoyltransferase 1 isoform X1 [KO:K00654] [EC:2.3.1.50]
101662398  SPTLC2; serine palmitoyltransferase 2 [KO:K00654] [EC:2.3.1.50]
101655232  SPTSSB; serine palmitoyltransferase small subunit B [KO:K26384]
101652276  serine palmitoyltransferase small subunit A [KO:K26384]
101640223  serine palmitoyltransferase small subunit A-like [KO:K26384]
101648049  CERS1; ceramide synthase 1 [KO:K04710] [EC:2.3.1.299]
101658541  CERS2; ceramide synthase 2 [KO:K24621] [EC:2.3.1.297]
101653374  CERS3; ceramide synthase 3 [KO:K24622] [EC:2.3.1.297 2.3.1.298]
101644034  CERS6; ceramide synthase 6 [KO:K23727] [EC:2.3.1.291]
101646397  CERS5; ceramide synthase 5 isoform X1 [KO:K23727] [EC:2.3.1.291]
101663265  DEGS2; sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
101649787  DEGS1; sphingolipid delta(4)-desaturase DES1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
101650417  SMPD1; sphingomyelin phosphodiesterase isoform X1 [KO:K12350] [EC:3.1.4.12]
101645512  SGMS2; phosphatidylcholine:ceramide cholinephosphotransferase 2 [KO:K04714] [EC:2.7.8.27]
101641498  SGMS1; phosphatidylcholine:ceramide cholinephosphotransferase 1 [KO:K04714] [EC:2.7.8.27]
101654642  TNF; tumor necrosis factor [KO:K03156]
101657422  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
101639474  NSMAF; protein FAN [KO:K18953]
101657696  SMPD2; sphingomyelin phosphodiesterase 2 [KO:K12351] [EC:3.1.4.12]
101655166  sphingomyelin phosphodiesterase 2-like [KO:K12351] [EC:3.1.4.12]
101659974  ASAH1; acid ceramidase isoform X1 [KO:K12348] [EC:3.5.1.23]
101645070  ASAH2; neutral ceramidase [KO:K12349] [EC:3.5.1.23]
101663034  ACER1; alkaline ceramidase 1 [KO:K01441] [EC:3.5.1.23]
101643616  ACER2; alkaline ceramidase 2 [KO:K01441] [EC:3.5.1.23]
101643813  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X3 [KO:K03171]
101643556  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
101654577  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
101659226  BID; BH3-interacting domain death agonist [KO:K04726]
101646711  BAX; apoptosis regulator BAX [KO:K02159]
101645193  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
101654493  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101653598  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
101645489  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
101657745  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
101656204  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
101653430  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
101653940  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
101661315  PRKCZ; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
101643102  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101649881  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
101655315  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101659722  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
101644319  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform-like [KO:K04382] [EC:3.1.3.16]
101644179  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101657344  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
101645417  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
101647744  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform-like [KO:K03456]
101663474  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
101662513  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
101662642  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
101657966  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
101659001  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
101660860  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
101659349  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
101651322  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X2 [KO:K11583]
101655698  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
101642174  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
101641890  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
101639916  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
101657070  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
101647784  LOW QUALITY PROTEIN: cellular tumor antigen p53-like [KO:K04451]
101656530  TP53; cellular tumor antigen p53 [KO:K04451]
101663465  FCER1A; high affinity immunoglobulin epsilon receptor subunit alpha [KO:K08089]
101641059  MS4A2; high affinity immunoglobulin epsilon receptor subunit beta [KO:K08090]
101658860  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
101664321  FYN; tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
101647958  GAB2; GRB2-associated-binding protein 2 [KO:K08091]
101641853  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101654217  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101640675  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101655654  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101659995  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101657368  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101646573  PLD1; phospholipase D1 isoform X2 [KO:K01115] [EC:3.1.4.4]
101662946  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
101653999  SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
101647651  SPHK2; sphingosine kinase 2 isoform X2 [KO:K04718] [EC:2.7.1.91]
101650277  KNG1; kininogen-1 isoform X1 [KO:K03898]
101639707  ADORA1; adenosine receptor A1 isoform X2 [KO:K04265]
101652471  ADORA3; adenosine receptor A3 [KO:K04268]
101662833  BDKRB2; B2 bradykinin receptor [KO:K03916]
101649402  OPRD1; delta-type opioid receptor [KO:K04213]
101658651  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
101643144  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
101641371  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
101651304  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
101650582  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
101647679  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
101656854  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X3 [KO:K05858] [EC:3.1.4.11]
101645703  PRKCE; protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
101648971  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101661786  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101643560  SGPP1; sphingosine-1-phosphate phosphatase 1 [KO:K04716] [EC:3.1.3.-]
101644553  SGPP2; sphingosine-1-phosphate phosphatase 2 [KO:K04717] [EC:3.1.3.-]
101643300  ABCC1; multidrug resistance-associated protein 1 [KO:K05665] [EC:7.6.2.3]
101638049  sphingosine-1-phosphate lyase 1-like [KO:K01634] [EC:4.1.2.27]
101663178  LOW QUALITY PROTEIN: sphingosine-1-phosphate lyase 1 [KO:K01634] [EC:4.1.2.27]
101650504  S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288]
101637926  S1PR2; sphingosine 1-phosphate receptor 2 [KO:K04292]
101663997  HRAS; GTPase HRas isoform X1 [KO:K02833]
101639926  KRAS; GTPase KRas isoform X3 [KO:K07827]
101649328  GTPase NRas-like [KO:K07828]
101653520  NRAS; GTPase NRas [KO:K07828]
101656360  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X3 [KO:K04366] [EC:2.7.11.1]
101650474  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101643986  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101661509  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
101644765  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
101644576  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
101656762  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
101660384  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
101651216  S1PR3; LOW QUALITY PROTEIN: sphingosine 1-phosphate receptor 3 [KO:K04290]
101637893  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101638289  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101657103  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
101651846  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
101662852  S1PR5; sphingosine 1-phosphate receptor 5 [KO:K04295]
101637962  GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
101645418  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
101662299  RHOA; transforming protein RhoA [KO:K04513]
101642345  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
101646611  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
101662652  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101663870  RELA; transcription factor p65 [KO:K04735]
Compound
C00065  L-Serine
C00154  Palmitoyl-CoA
C00165  Diacylglycerol
C00195  N-Acylsphingosine
C00212  Adenosine
C00319  Sphingosine
C00346  Ethanolamine phosphate
C00533  Nitric oxide
C00550  Sphingomyelin
C00836  Sphinganine
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
C06124  Sphingosine 1-phosphate
C12126  Dihydroceramide
C16845  Peroxynitrite
Reference
PMID:18216770
  Authors
Hannun YA, Obeid LM
  Title
Principles of bioactive lipid signalling: lessons from sphingolipids.
  Journal
Nat Rev Mol Cell Biol 9:139-50 (2008)
DOI:10.1038/nrm2329
Reference
PMID:17161984
  Authors
Taha TA, Mullen TD, Obeid LM
  Title
A house divided: ceramide, sphingosine, and sphingosine-1-phosphate in programmed cell death.
  Journal
Biochim Biophys Acta 1758:2027-36 (2006)
DOI:10.1016/j.bbamem.2006.10.018
Reference
PMID:23919551
  Authors
Liu J, Beckman BS, Foroozesh M
  Title
A review of ceramide analogs as potential anticancer agents.
  Journal
Future Med Chem 5:1405-21 (2013)
DOI:10.4155/fmc.13.107
Reference
PMID:18675379
  Authors
Kono M, Allende ML, Proia RL
  Title
Sphingosine-1-phosphate regulation of mammalian development.
  Journal
Biochim Biophys Acta 1781:435-41 (2008)
DOI:10.1016/j.bbalip.2008.07.001
Reference
PMID:18403224
  Authors
Olivera A
  Title
Unraveling the complexities of sphingosine-1-phosphate function: the mast cell model.
  Journal
Prostaglandins Other Lipid Mediat 86:1-11 (2008)
DOI:10.1016/j.prostaglandins.2008.02.005
Reference
PMID:25309325
  Authors
Brunkhorst R, Vutukuri R, Pfeilschifter W
  Title
Fingolimod for the treatment of neurological diseases-state of play and future perspectives.
  Journal
Front Cell Neurosci 8:283 (2014)
DOI:10.3389/fncel.2014.00283
Reference
PMID:15999095
  Authors
Rosen H, Goetzl EJ
  Title
Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network.
  Journal
Nat Rev Immunol 5:560-70 (2005)
DOI:10.1038/nri1650
Reference
PMID:10880336
  Authors
Pyne S, Pyne NJ
  Title
Sphingosine 1-phosphate signalling in mammalian cells.
  Journal
Biochem J 349:385-402 (2000)
DOI:10.1042/bj3490385
Reference
PMID:21705677
  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
Am J Physiol Heart Circ Physiol 301:H1487-95 (2011)
DOI:10.1152/ajpheart.01003.2010
Reference
PMID:15451787
  Authors
Jin ZQ, Goetzl EJ, Karliner JS
  Title
Sphingosine kinase activation mediates ischemic preconditioning in murine heart.
  Journal
Circulation 110:1980-9 (2004)
DOI:10.1161/01.CIR.0000143632.06471.93
Reference
PMID:17913601
  Authors
Melendez AJ
  Title
Sphingosine kinase signalling in immune cells: potential as novel therapeutic targets.
  Journal
Biochim Biophys Acta 1784:66-75 (2008)
DOI:10.1016/j.bbapap.2007.07.013
Reference
PMID:22654878
  Authors
Halova I, Draberova L, Draber P
  Title
Mast cell chemotaxis - chemoattractants and signaling pathways.
  Journal
Front Immunol 3:119 (2012)
DOI:10.3389/fimmu.2012.00119
Reference
PMID:17438574
  Authors
Kraft S, Kinet JP
  Title
New developments in FcepsilonRI regulation, function and inhibition.
  Journal
Nat Rev Immunol 7:365-78 (2007)
DOI:10.1038/nri2072
Reference
PMID:16470226
  Authors
Gilfillan AM, Tkaczyk C.
  Title
Integrated signalling pathways for mast-cell activation.
  Journal
Nat Rev Immunol 6:218-30 (2006)
DOI:10.1038/nri1782
Reference
PMID:11418646
  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
J Immunol 167:173-80 (2001)
DOI:10.4049/jimmunol.167.1.173
Reference
PMID:20534702
  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
J Leukoc Biol 88:897-903 (2010)
DOI:10.1189/jlb.0410188
Reference
PMID:11001563
  Authors
Chatterjee S
  Title
Neutral sphingomyelinase: past, present and future.
  Journal
Chem Phys Lipids 102:79-96 (1999)
DOI:10.1016/S0009-3084(99)00077-8
Related
pathway
etf00600  Sphingolipid metabolism
etf04010  MAPK signaling pathway
etf04142  Lysosome
etf04151  PI3K-Akt signaling pathway
KO pathway
ko04071   
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