KEGG   PATHWAY: ray04071
Entry
ray04071                    Pathway                                
Name
Sphingolipid signaling pathway - Rousettus aegyptiacus (Egyptian rousette)
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
ray04071  Sphingolipid signaling pathway
ray04071

Organism
Rousettus aegyptiacus (Egyptian rousette) [GN:ray]
Gene
107507111  SPTLC3; serine palmitoyltransferase 3 [KO:K00654] [EC:2.3.1.50]
107518642  SPTLC1; serine palmitoyltransferase 1 isoform X1 [KO:K00654] [EC:2.3.1.50]
107516662  SPTLC2; serine palmitoyltransferase 2 isoform X1 [KO:K00654] [EC:2.3.1.50]
107512799  SPTSSA; serine palmitoyltransferase small subunit A [KO:K26384]
107513074  SPTSSB; serine palmitoyltransferase small subunit B [KO:K26384]
107503723  CERS1; ceramide synthase 1 [KO:K04710] [EC:2.3.1.299]
107499037  CERS2; ceramide synthase 2 isoform X1 [KO:K24621] [EC:2.3.1.297]
107519920  CERS4; ceramide synthase 4 isoform X1 [KO:K24621] [EC:2.3.1.297]
107515791  CERS3; ceramide synthase 3 isoform X1 [KO:K24622] [EC:2.3.1.297 2.3.1.298]
107521030  CERS6; ceramide synthase 6 isoform X1 [KO:K23727] [EC:2.3.1.291]
107514286  CERS5; ceramide synthase 5 [KO:K23727] [EC:2.3.1.291]
107521085  DEGS1; sphingolipid delta(4)-desaturase DES1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
107497563  DEGS2; sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 isoform X1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
107504370  SMPD1; sphingomyelin phosphodiesterase [KO:K12350] [EC:3.1.4.12]
107515499  SGMS1; LOW QUALITY PROTEIN: phosphatidylcholine:ceramide cholinephosphotransferase 1 [KO:K04714] [EC:2.7.8.27]
107518804  SGMS2; phosphatidylcholine:ceramide cholinephosphotransferase 2 [KO:K04714] [EC:2.7.8.27]
107498497  TNF; tumor necrosis factor [KO:K03156]
107519788  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
107521185  NSMAF; protein FAN isoform X1 [KO:K18953]
107518493  SMPD2; sphingomyelin phosphodiesterase 2 [KO:K12351] [EC:3.1.4.12]
107502652  ASAH1; acid ceramidase [KO:K12348] [EC:3.5.1.23]
107515497  ASAH2; neutral ceramidase isoform X1 [KO:K12349] [EC:3.5.1.23]
107518599  ACER2; alkaline ceramidase 2 [KO:K01441] [EC:3.5.1.23]
107511083  ACER1; alkaline ceramidase 1 [KO:K01441] [EC:3.5.1.23]
107520081  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
107503081  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
107513216  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
107500447  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
107498831  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
107521291  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
107512328  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
107509910  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
107515392  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
107497883  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
107497895  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
107500264  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
107500274  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
107510685  PRKCZ; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
107513978  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
107521783  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107498395  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
107503915  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
107506800  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
107505807  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
107521184  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
107500417  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
107519027  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
107515450  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
107500870  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
107514412  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
107505863  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
107508495  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
107509328  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
107517041  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
107521366  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
107521621  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
107501966  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
107515689  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
107503182  FCER1A; high affinity immunoglobulin epsilon receptor subunit alpha [KO:K08089]
107497359  MS4A2; high affinity immunoglobulin epsilon receptor subunit beta [KO:K08090]
107504680  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma isoform X1 [KO:K07983]
107506307  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
107519146  GAB2; GRB2-associated-binding protein 2 [KO:K08091]
107520152  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
107517828  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
107513958  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
107521668  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
107517899  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
107498704  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
107515926  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
107509491  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
107501245  SPHK1; sphingosine kinase 1 isoform X1 [KO:K04718] [EC:2.7.1.91]
107498846  SPHK2; sphingosine kinase 2 isoform X1 [KO:K04718] [EC:2.7.1.91]
107505885  KNG1; kininogen-1 isoform X1 [KO:K03898]
107503000  ADORA1; adenosine receptor A1 [KO:K04265]
107499863  adenosine receptor A3 [KO:K04268]
107503595  OPRD1; delta-type opioid receptor [KO:K04213]
107516134  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
107518173  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
107513376  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
107506114  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
107519930  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
107497081  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
107514464  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
107509571  PRKCE; protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
107515836  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
107497830  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
107509326  SGPP1; sphingosine-1-phosphate phosphatase 1 [KO:K04716] [EC:3.1.3.-]
107516746  SGPP2; sphingosine-1-phosphate phosphatase 2 isoform X1 [KO:K04717] [EC:3.1.3.-]
107516824  ABCC1; multidrug resistance-associated protein 1 isoform X1 [KO:K05665] [EC:7.6.2.3]
107498214  SGPL1; sphingosine-1-phosphate lyase 1 isoform X1 [KO:K01634] [EC:4.1.2.27]
107504393  S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288]
107515121  S1PR2; sphingosine 1-phosphate receptor 2 [KO:K04292]
107507127  HRAS; GTPase HRas isoform X1 [KO:K02833]
107497434  KRAS; GTPase KRas isoform X1 [KO:K07827]
107499847  NRAS; LOW QUALITY PROTEIN: GTPase NRas [KO:K07828]
107519729  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
107508942  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
107510634  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
107498762  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
107520319  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
107515925  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
107519267  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
107520254  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
107504309  S1PR3; sphingosine 1-phosphate receptor 3 [KO:K04290]
107517194  GNAQ; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
107510307  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
107516091  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
107503061  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
107520106  S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293]
107515113  S1PR5; sphingosine 1-phosphate receptor 5 isoform X1 [KO:K04295]
107521430  GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
107510298  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
107513350  RHOA; transforming protein RhoA [KO:K04513]
107520580  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
107501194  ROCK2; LOW QUALITY PROTEIN: rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.1]
107501760  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
107517900  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
107497522  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
ray00600  Sphingolipid metabolism
ray04010  MAPK signaling pathway
ray04142  Lysosome
ray04151  PI3K-Akt signaling pathway
KO pathway
ko04071   
LinkDB

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