KEGG   PATHWAY: bbis04071
Entry
bbis04071                   Pathway                                
Name
Sphingolipid signaling pathway - Bison bison bison (American bison)
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
bbis04071  Sphingolipid signaling pathway
bbis04071

Organism
Bison bison bison (American bison) [GN:bbis]
Gene
104985683  SPTLC1; serine palmitoyltransferase 1 [KO:K00654] [EC:2.3.1.50]
104991789  SPTLC2; serine palmitoyltransferase 2 [KO:K00654] [EC:2.3.1.50]
104991603  SPTLC3; serine palmitoyltransferase 3 [KO:K00654] [EC:2.3.1.50]
104988485  SPTSSB; serine palmitoyltransferase small subunit B [KO:K26384]
104993866  CERS1; ceramide synthase 1 isoform X1 [KO:K04710] [EC:2.3.1.299]
104979757  CERS4; ceramide synthase 4 [KO:K24621] [EC:2.3.1.297]
104987650  CERS2; ceramide synthase 2 [KO:K24621] [EC:2.3.1.297]
104992832  CERS3; ceramide synthase 3 [KO:K24622] [EC:2.3.1.297 2.3.1.298]
105001498  CERS5; ceramide synthase 5 [KO:K23727] [EC:2.3.1.291]
105002359  CERS6; ceramide synthase 6 isoform X1 [KO:K23727] [EC:2.3.1.291]
104996962  DEGS2; sphingolipid delta(4)-desaturase/C4-hydroxylase DES2 isoform X1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
104997878  DEGS1; sphingolipid delta(4)-desaturase DES1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
104988012  SMPD1; sphingomyelin phosphodiesterase [KO:K12350] [EC:3.1.4.12]
104982767  SGMS1; phosphatidylcholine:ceramide cholinephosphotransferase 1 [KO:K04714] [EC:2.7.8.27]
105002092  SGMS2; phosphatidylcholine:ceramide cholinephosphotransferase 2 [KO:K04714] [EC:2.7.8.27]
104983770  TNF; tumor necrosis factor isoform X1 [KO:K03156]
104992338  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
104987891  NSMAF; protein FAN [KO:K18953]
105000660  SMPD2; sphingomyelin phosphodiesterase 2 [KO:K12351] [EC:3.1.4.12]
105001915  ASAH1; acid ceramidase [KO:K12348] [EC:3.5.1.23]
104982770  ASAH2; neutral ceramidase [KO:K12349] [EC:3.5.1.23]
104979914  ACER1; alkaline ceramidase 1 [KO:K01441] [EC:3.5.1.23]
105000954  ACER2; alkaline ceramidase 2 isoform X1 [KO:K01441] [EC:3.5.1.23]
104996716  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
104982944  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
104992248  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
104992258  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
104995631  BAX; apoptosis regulator BAX [KO:K02159]
104991715  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
104998999  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
104992939  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
104981526  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
104981967  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
104981977  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
104994938  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
104994939  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
104995923  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
104986245  RAC-gamma serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
104995356  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104989637  RAC-alpha serine/threonine-protein kinase-like [KO:K04456] [EC:2.7.11.1]
105003597  RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
104999231  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
104991861  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
104987748  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
104995460  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
105005078  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform [KO:K03456]
104982191  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
104994293  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
104988728  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
104996269  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
105002745  PPP2R2D; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
104981835  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta [KO:K11583]
105001822  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
104985235  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
104998031  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
105005228  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
104987202  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
104993494  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
104996946  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
104990761  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
104993542  FCER1A; high affinity immunoglobulin epsilon receptor subunit alpha isoform X1 [KO:K08089]
104991299  MS4A2; high affinity immunoglobulin epsilon receptor subunit beta isoform X1 [KO:K08090]
104984070  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
105000638  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
104998160  GAB2; GRB2-associated-binding protein 2 [KO:K08091]
104999978  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105001799  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
104996058  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
104998445  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
104992716  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
104994333  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
104993960  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
104985201  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
105000373  SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
104995615  SPHK2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
104998627  KNG1; kininogen-1 isoform X1 [KO:K03898]
104998778  ADORA1; adenosine receptor A1 [KO:K04265]
104996977  BDKRB2; B2 bradykinin receptor [KO:K03916]
104981264  OPRD1; delta-type opioid receptor [KO:K04213]
104981671  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
104994506  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
104997186  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
104987189  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
104994462  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
104984484  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
104984486  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
104987605  PRKCE; protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
104986748  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
104995620  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104993515  SGPP1; sphingosine-1-phosphate phosphatase 1 [KO:K04716] [EC:3.1.3.-]
104986515  SGPP2; sphingosine-1-phosphate phosphatase 2 [KO:K04717] [EC:3.1.3.-]
104988538  ABCC1; multidrug resistance-associated protein 1 isoform X1 [KO:K05665] [EC:7.6.2.3]
104997553  SGPL1; sphingosine-1-phosphate lyase 1 [KO:K01634] [EC:4.1.2.27]
104981718  S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288]
104979837  S1PR2; sphingosine 1-phosphate receptor 2 [KO:K04292]
105003692  HRAS; GTPase HRas [KO:K02833]
105000225  KRAS; GTPase KRas isoform X1 [KO:K07827]
104981582  NRAS; GTPase NRas [KO:K07828]
105004742  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
104984678  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
104979900  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
104988870  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
105001191  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
104992794  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
105003447  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
105000595  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
104992062  S1PR3; sphingosine 1-phosphate receptor 3 isoform X1 [KO:K04290]
104996774  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
105000525  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
104986737  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
105000236  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
104979886  S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293]
104979821  S1PR5; sphingosine 1-phosphate receptor 5 [KO:K04295]
105002254  GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
105000283  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
104997209  RHOA; transforming protein RhoA [KO:K04513]
104980280  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
104997365  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
104987508  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]
104994637  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
104987029  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
bbis00600  Sphingolipid metabolism
bbis04010  MAPK signaling pathway
bbis04142  Lysosome
bbis04151  PI3K-Akt signaling pathway
KO pathway
ko04071   
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