KEGG   PATHWAY: pkl04071
Entry
pkl04071                    Pathway                                
Name
Sphingolipid signaling pathway - Pipistrellus kuhlii (Kuhl's pipistrelle)
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
pkl04071  Sphingolipid signaling pathway
pkl04071

Organism
Pipistrellus kuhlii (Kuhl's pipistrelle) [GN:pkl]
Gene
118714774  SPTLC1; serine palmitoyltransferase 1 isoform X1 [KO:K00654] [EC:2.3.1.50]
118714820  SPTLC2; serine palmitoyltransferase 2 isoform X1 [KO:K00654] [EC:2.3.1.50]
118707583  SPTLC3; serine palmitoyltransferase 3 isoform X1 [KO:K00654] [EC:2.3.1.50]
118726599  SPTSSA; serine palmitoyltransferase small subunit A [KO:K26384]
118723923  SPTSSB; serine palmitoyltransferase small subunit B [KO:K26384]
118726060  CERS1; ceramide synthase 1 isoform X1 [KO:K04710] [EC:2.3.1.299]
118727471  CERS2; ceramide synthase 2 isoform X1 [KO:K24621] [EC:2.3.1.297]
118725975  CERS4; ceramide synthase 4 isoform X1 [KO:K24621] [EC:2.3.1.297]
118704309  CERS3; ceramide synthase 3 isoform X1 [KO:K24622] [EC:2.3.1.297 2.3.1.298]
118729927  CERS5; ceramide synthase 5 isoform X1 [KO:K23727] [EC:2.3.1.291]
118709783  CERS6; ceramide synthase 6 isoform X1 [KO:K23727] [EC:2.3.1.291]
118727624  DEGS1; sphingolipid delta(4)-desaturase DES1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
118704263  DEGS2; sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
118713587  SMPD1; sphingomyelin phosphodiesterase [KO:K12350] [EC:3.1.4.12]
118719254  SGMS1; phosphatidylcholine:ceramide cholinephosphotransferase 1 isoform X1 [KO:K04714] [EC:2.7.8.27]
118702959  SGMS2; phosphatidylcholine:ceramide cholinephosphotransferase 2 [KO:K04714] [EC:2.7.8.27]
118716986  TNF; tumor necrosis factor [KO:K03156]
118728672  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
118718286  NSMAF; protein FAN isoform X1 [KO:K18953]
118705619  SMPD2; sphingomyelin phosphodiesterase 2 isoform X1 [KO:K12351] [EC:3.1.4.12]
118730877  ASAH1; acid ceramidase [KO:K12348] [EC:3.5.1.23]
118719252  ASAH2; neutral ceramidase isoform X1 [KO:K12349] [EC:3.5.1.23]
118731247  ACER1; alkaline ceramidase 1 isoform X1 [KO:K01441] [EC:3.5.1.23]
118716613  ACER2; alkaline ceramidase 2 isoform X1 [KO:K01441] [EC:3.5.1.23]
118707045  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
118713962  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
118728790  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
118712174  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
118705482  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
118728660  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
118732117  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
118725940  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
118705126  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
118705127  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
118714740  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
118714741  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
118732016  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
118727672  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118714856  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
118702383  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
118707440  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
118711891  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
118730354  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
118713302  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
118710227  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
118719575  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
118711873  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
118709062  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
118725910  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
118715311  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
118726726  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
118704251  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
118705241  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
118721526  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
118714938  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
118716992  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
118726809  TP53; cellular tumor antigen p53 [KO:K04451]
118721592  FCER1A; high affinity immunoglobulin epsilon receptor subunit alpha [KO:K08089]
118713704  MS4A2; high affinity immunoglobulin epsilon receptor subunit beta isoform X1 [KO:K08090]
118716888  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
118705144  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
118713600  GAB2; GRB2-associated-binding protein 2 isoform X1 [KO:K08091]
118722506  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118715291  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118731984  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118703803  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
118722550  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
118725879  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
118722696  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
118727000  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
118704513  SPHK1; LOW QUALITY PROTEIN: sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
118721086  SPHK2; sphingosine kinase 2 isoform X1 [KO:K04718] [EC:2.7.1.91]
118724652  KNG1; kininogen-1 isoform X1 [KO:K03898]
118724654  kininogen-1-like [KO:K03898]
118724655  kininogen-1-like [KO:K03898]
118710529  ADORA1; adenosine receptor A1 [KO:K04265]
118727500  ADORA3; adenosine receptor A3 isoform X1 [KO:K04268]
118714109  BDKRB2; B2 bradykinin receptor [KO:K03916]
118724381  OPRD1; delta-type opioid receptor [KO:K04213]
118714364  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
118715646  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
118727148  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
118707269  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
118707553  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
118723641  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
118708478  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
118717316  PRKCE; protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
118704886  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
118725266  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
118716981  SGPP1; sphingosine-1-phosphate phosphatase 1 [KO:K04716] [EC:3.1.3.-]
118709056  SGPP2; sphingosine-1-phosphate phosphatase 2 [KO:K04717] [EC:3.1.3.-]
118703929  ABCC1; multidrug resistance-associated protein 1 isoform X1 [KO:K05665] [EC:7.6.2.3]
118719138  SGPL1; sphingosine-1-phosphate lyase 1 [KO:K01634] [EC:4.1.2.27]
118727199  S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288]
118731234  S1PR2; sphingosine 1-phosphate receptor 2 [KO:K04292]
118717957  HRAS; GTPase HRas [KO:K02833]
118730853  KRAS; GTPase KRas isoform X1 [KO:K07827]
118727253  NRAS; GTPase NRas [KO:K07828]
118715231  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
118731837  LOW QUALITY PROTEIN: RAF proto-oncogene serine/threonine-protein kinase-like [KO:K04366] [EC:2.7.11.1]
118719104  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
118731359  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
118702963  PDPK1; LOW QUALITY PROTEIN: 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
118704763  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
118710908  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
118730331  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
118704565  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
118708685  S1PR3; sphingosine 1-phosphate receptor 3 [KO:K04290]
118716462  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
118726595  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
118731558  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
118719731  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
118731316  S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293]
118731204  S1PR5; sphingosine 1-phosphate receptor 5 isoform X1 [KO:K04295]
118711380  GNA12; guanine nucleotide-binding protein subunit alpha-12 isoform X1 [KO:K04346]
118726223  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
118703292  transforming protein RhoA-like [KO:K04513]
118715172  transforming protein RhoA-like isoform X1 [KO:K04513]
118715673  RHOA; transforming protein RhoA [KO:K04513]
118707729  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
118717047  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
118719258  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]
118703354  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
118706879  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
pkl00600  Sphingolipid metabolism
pkl04010  MAPK signaling pathway
pkl04142  Lysosome
pkl04151  PI3K-Akt signaling pathway
KO pathway
ko04071   
LinkDB

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