KEGG   PATHWAY: myb04071
Entry
myb04071                    Pathway                                
Name
Sphingolipid signaling pathway - Myotis brandtii (Brandt's 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
myb04071  Sphingolipid signaling pathway
myb04071

Organism
Myotis brandtii (Brandt's bat) [GN:myb]
Gene
102253057  SPTLC1; serine palmitoyltransferase long chain base subunit 1 [KO:K00654] [EC:2.3.1.50]
102260758  SPTLC2; serine palmitoyltransferase long chain base subunit 2 [KO:K00654] [EC:2.3.1.50]
102260066  SPTLC3; serine palmitoyltransferase long chain base subunit 3 [KO:K00654] [EC:2.3.1.50]
102247049  SPTSSB; serine palmitoyltransferase small subunit B [KO:K26384]
102249252  CERS1; ceramide synthase 1 [KO:K04710] [EC:2.3.1.299]
102256999  CERS2; ceramide synthase 2 [KO:K24621] [EC:2.3.1.297]
102250642  CERS4; ceramide synthase 4 [KO:K24621] [EC:2.3.1.297]
102242969  CERS3; ceramide synthase 3 [KO:K24622] [EC:2.3.1.297 2.3.1.298]
102246479  CERS6; ceramide synthase 6 [KO:K23727] [EC:2.3.1.291]
102262839  CERS5; ceramide synthase 5 [KO:K23727] [EC:2.3.1.291]
102260316  DEGS1; delta 4-desaturase, sphingolipid 1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
102251258  DEGS2; delta 4-desaturase, sphingolipid 2 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
102255688  SMPD1; sphingomyelin phosphodiesterase 1 [KO:K12350] [EC:3.1.4.12]
102257109  SGMS2; sphingomyelin synthase 2 [KO:K04714] [EC:2.7.8.27]
102255621  SGMS1; sphingomyelin synthase 1 [KO:K04714] [EC:2.7.8.27]
102246703  TNF; tumor necrosis factor [KO:K03156]
102251038  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
102240024  NSMAF; neutral sphingomyelinase activation associated factor [KO:K18953]
102252179  SMPD2; sphingomyelin phosphodiesterase 2 [KO:K12351] [EC:3.1.4.12]
102261355  ASAH1; N-acylsphingosine amidohydrolase 1 [KO:K12348] [EC:3.5.1.23]
102263955  ASAH2; N-acylsphingosine amidohydrolase 2 [KO:K12349] [EC:3.5.1.23]
102248194  ACER2; alkaline ceramidase 2 [KO:K01441] [EC:3.5.1.23]
102250405  ACER1; alkaline ceramidase 1 [KO:K01441] [EC:3.5.1.23]
102247104  TRADD; TNFRSF1A associated via death domain [KO:K03171]
102263277  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
102255890  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
102238957  BID; BH3 interacting domain death agonist [KO:K04726]
106723573  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
102256847  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
102259984  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
102263026  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102246292  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
102254628  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102248097  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102254920  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
106723559  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102238785  PRKCZ; protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
106726938  protein kinase C zeta type-like [KO:K18952] [EC:2.7.11.13]
102250265  protein kinase C zeta type-like [KO:K18952] [EC:2.7.11.13]
102254864  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102254191  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102251050  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102248597  BCL2; BCL2, apoptosis regulator [KO:K02161]
102246010  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
102255371  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
102262643  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
102254517  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
102243537  PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
102240425  PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
102238990  PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
102254637  PPP2R2D; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354]
102248512  PPP2R3C; protein phosphatase 2 regulatory subunit B''gamma [KO:K11583]
106725200  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta-like [KO:K11583]
102240816  PPP2R3A; protein phosphatase 2 regulatory subunit B''alpha [KO:K11583]
102241218  PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
102242374  PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
102239026  PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
102249194  PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
102244211  PPP2R5B; protein phosphatase 2 regulatory subunit B'beta [KO:K11584]
102244768  TP53; tumor protein p53 [KO:K04451]
102252052  FCER1A; Fc fragment of IgE receptor Ia [KO:K08089]
102242504  MS4A2; membrane spanning 4-domains A2 [KO:K08090]
102246191  FCER1G; Fc fragment of IgE receptor Ig [KO:K07983]
102242533  FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]
102256059  GAB2; GRB2 associated binding protein 2 [KO:K08091]
102260487  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102252921  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102239669  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
102258430  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102253405  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102242302  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102264100  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
102239050  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
102255740  SPHK2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
102254173  SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
102242693  KNG1; kininogen 1 [KO:K03898]
102247581  kininogen-1 [KO:K03898]
102246781  kininogen-1 [KO:K03898]
102242144  ADORA1; adenosine A1 receptor [KO:K04265]
102261536  ADORA3; adenosine A3 receptor [KO:K04268]
102249334  BDKRB2; bradykinin receptor B2 [KO:K03916]
102239230  OPRD1; opioid receptor delta 1 [KO:K04213]
102249318  GNAI2; G protein subunit alpha i2 [KO:K04630]
102239557  GNAI3; G protein subunit alpha i3 [KO:K04630]
102256872  GNAI1; G protein subunit alpha i1 [KO:K04630]
102238655  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
102254054  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102241255  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102240650  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102263707  PRKCE; protein kinase C epsilon [KO:K18050] [EC:2.7.11.13]
102255250  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102245641  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102253110  SGPP1; sphingosine-1-phosphate phosphatase 1 [KO:K04716] [EC:3.1.3.-]
102259379  SGPP2; sphingosine-1-phosphate phosphatase 2 [KO:K04717] [EC:3.1.3.-]
102239517  ABCC1; ATP binding cassette subfamily C member 1 [KO:K05665] [EC:7.6.2.3]
102240699  SGPL1; sphingosine-1-phosphate lyase 1 [KO:K01634] [EC:4.1.2.27]
102248074  S1PR1; sphingosine-1-phosphate receptor 1 [KO:K04288]
102242018  S1PR2; sphingosine-1-phosphate receptor 2 [KO:K04292]
102263667  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102244940  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102247606  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102254003  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102240696  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102245571  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102262391  PDPK1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
102256555  NOS3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
102259160  RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
102239988  RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
102249503  RAC3; ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [KO:K07861]
102239166  S1PR3; sphingosine-1-phosphate receptor 3 [KO:K04290]
102247263  GNAQ; G protein subunit alpha q [KO:K04634]
102260557  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
102243136  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
102249897  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
102259649  S1PR4; sphingosine-1-phosphate receptor 4 [KO:K04293]
102260289  GNA12; G protein subunit alpha 12 [KO:K04346]
102252423  GNA13; G protein subunit alpha 13 [KO:K04639]
102244315  RHOA; ras homolog family member A [KO:K04513]
102252747  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.1]
102254781  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.1]
102257838  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
102255251  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102263790  RELA; RELA proto-oncogene, NF-kB subunit [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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
myb00600  Sphingolipid metabolism
myb04010  MAPK signaling pathway
myb04142  Lysosome
myb04151  PI3K-Akt signaling pathway
KO pathway
ko04071   
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