KEGG   PATHWAY: hai04071
Entry
hai04071                    Pathway                                
Name
Sphingolipid signaling pathway - Hipposideros armiger (great roundleaf bat)
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
hai04071  Sphingolipid signaling pathway
hai04071

Organism
Hipposideros armiger (great roundleaf bat) [GN:hai]
Gene
109381600  SPTLC2; serine palmitoyltransferase 2 [KO:K00654] [EC:2.3.1.50]
109378966  SPTLC3; serine palmitoyltransferase 3 [KO:K00654] [EC:2.3.1.50]
109396678  SPTLC1; serine palmitoyltransferase 1 isoform X1 [KO:K00654] [EC:2.3.1.50]
109376539  SPTSSA; serine palmitoyltransferase small subunit A [KO:K26384]
109373119  SPTSSB; serine palmitoyltransferase small subunit B [KO:K26384]
109382399  CERS1; ceramide synthase 1 [KO:K04710] [EC:2.3.1.299]
109372275  CERS2; ceramide synthase 2 isoform X1 [KO:K24621] [EC:2.3.1.297]
109396095  CERS4; ceramide synthase 4 isoform X1 [KO:K24621] [EC:2.3.1.297]
109380354  CERS3; ceramide synthase 3 [KO:K24622] [EC:2.3.1.297 2.3.1.298]
109390309  CERS6; ceramide synthase 6 isoform X1 [KO:K23727] [EC:2.3.1.291]
109393272  CERS5; ceramide synthase 5 isoform X1 [KO:K23727] [EC:2.3.1.291]
109381071  DEGS2; sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 isoform X1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
109381186  DEGS1; sphingolipid delta(4)-desaturase DES1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
109376525  SMPD1; sphingomyelin phosphodiesterase [KO:K12350] [EC:3.1.4.12]
109379483  SGMS2; phosphatidylcholine:ceramide cholinephosphotransferase 2 [KO:K04714] [EC:2.7.8.27]
109387531  SGMS1; phosphatidylcholine:ceramide cholinephosphotransferase 1 [KO:K04714] [EC:2.7.8.27]
109373073  TNF; tumor necrosis factor isoform X1 [KO:K03156]
109373644  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
109376138  NSMAF; protein FAN isoform X1 [KO:K18953]
109391424  SMPD2; sphingomyelin phosphodiesterase 2 [KO:K12351] [EC:3.1.4.12]
109394586  ASAH1; acid ceramidase [KO:K12348] [EC:3.5.1.23]
109387522  ASAH2; neutral ceramidase [KO:K12349] [EC:3.5.1.23]
109377289  alkaline ceramidase 2-like [KO:K01441] [EC:3.5.1.23]
109391488  ACER2; alkaline ceramidase 2 isoform X1 [KO:K01441] [EC:3.5.1.23]
109388589  ACER1; alkaline ceramidase 1 [KO:K01441] [EC:3.5.1.23]
109390108  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
109381672  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
109395931  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
109373303  BID; BH3-interacting domain death agonist [KO:K04726]
109391068  BAX; apoptosis regulator BAX [KO:K02159]
109385622  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
109392215  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
109377948  mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
109392748  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
109395979  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
109395980  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
109396629  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
109396630  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
109391154  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
109381083  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109385878  RAC-beta serine/threonine-protein kinase-like isoform X1 [KO:K04456] [EC:2.7.11.1]
109374859  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
109385353  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
109390784  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
109382627  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
109382969  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
109388695  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
109377484  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
109392769  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform-like [KO:K04354]
109391741  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
109374120  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
109383556  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
109375567  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
109383886  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
109389233  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
109381056  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
109379146  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
109384306  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
109382865  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
109375911  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
109394672  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
109377563  FCER1A; high affinity immunoglobulin epsilon receptor subunit alpha [KO:K08089]
109390007  MS4A2; high affinity immunoglobulin epsilon receptor subunit beta [KO:K08090]
109376936  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
109384758  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
109371247  GAB2; GRB2-associated-binding protein 2 [KO:K08091]
109381238  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
109394108  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
109372681  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
109382484  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
109395865  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
109373811  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
109394696  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
109371666  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
109391059  SPHK2; sphingosine kinase 2 isoform X1 [KO:K04718] [EC:2.7.1.91]
109383749  SPHK1; sphingosine kinase 1 isoform X1 [KO:K04718] [EC:2.7.1.91]
109371464  KNG1; kininogen-1 isoform X1 [KO:K03898]
109380484  ADORA1; adenosine receptor A1 isoform X1 [KO:K04265]
109382719  BDKRB2; B2 bradykinin receptor [KO:K03916]
109392435  OPRD1; delta-type opioid receptor [KO:K04213]
109377665  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
109375288  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
109392892  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
109378976  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
109378977  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
109384329  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
109383976  PLCB2; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
109393868  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
109385803  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
109394900  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109375914  SGPP1; sphingosine-1-phosphate phosphatase 1 isoform X1 [KO:K04716] [EC:3.1.3.-]
109396189  SGPP2; sphingosine-1-phosphate phosphatase 2 isoform X1 [KO:K04717] [EC:3.1.3.-]
109395236  ABCC1; multidrug resistance-associated protein 1 [KO:K05665] [EC:7.6.2.3]
109372259  SGPL1; sphingosine-1-phosphate lyase 1 [KO:K01634] [EC:4.1.2.27]
109371358  S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288]
109391638  S1PR2; sphingosine 1-phosphate receptor 2 [KO:K04292]
109375639  HRAS; GTPase HRas isoform X1 [KO:K02833]
109385150  GTPase HRas-like [KO:K02833]
109389264  KRAS; GTPase KRas isoform X1 [KO:K07827]
109377015  NRAS; GTPase NRas [KO:K07828]
109384548  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
109385252  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
109388626  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
109385875  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
109389680  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
109380150  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
109394502  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
109393041  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
109376925  S1PR3; sphingosine 1-phosphate receptor 3 [KO:K04290]
109385746  guanine nucleotide-binding protein G(q) subunit alpha-like [KO:K04634]
109380289  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
109386578  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
109372505  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
109388553  S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293]
109391650  S1PR5; sphingosine 1-phosphate receptor 5 [KO:K04295]
109380223  GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
109380315  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
109376114  RHOA; transforming protein RhoA isoform X1 [KO:K04513]
109388840  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
109386644  ROCK2; rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.1]
109387530  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN isoform X1 [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
109372541  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
109384322  RELA; transcription factor p65 isoform X1 [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
hai00600  Sphingolipid metabolism
hai04010  MAPK signaling pathway
hai04142  Lysosome
hai04151  PI3K-Akt signaling pathway
KO pathway
ko04071   
LinkDB

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