KEGG   PATHWAY: rbb04071
Entry
rbb04071                    Pathway                                
Name
Sphingolipid signaling pathway - Rhinopithecus bieti (black snub-nosed monkey)
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
rbb04071  Sphingolipid signaling pathway
rbb04071

Organism
Rhinopithecus bieti (black snub-nosed monkey) [GN:rbb]
Gene
108516811  SPTLC1; serine palmitoyltransferase 1 [KO:K00654] [EC:2.3.1.50]
108527781  SPTLC3; serine palmitoyltransferase 3 isoform X1 [KO:K00654] [EC:2.3.1.50]
108534968  SPTLC2; serine palmitoyltransferase 2 [KO:K00654] [EC:2.3.1.50]
108544674  SPTSSA; serine palmitoyltransferase small subunit A [KO:K26384]
108513218  SPTSSB; serine palmitoyltransferase small subunit B [KO:K26384]
108513104  serine palmitoyltransferase small subunit B-like [KO:K26384]
108515632  CERS1; ceramide synthase 1 isoform X1 [KO:K04710] [EC:2.3.1.299]
108533256  CERS2; ceramide synthase 2 [KO:K24621] [EC:2.3.1.297]
108534518  CERS4; ceramide synthase 4 [KO:K24621] [EC:2.3.1.297]
108512618  CERS3; ceramide synthase 3 [KO:K24622] [EC:2.3.1.297 2.3.1.298]
108520506  CERS6; ceramide synthase 6 [KO:K23727] [EC:2.3.1.291]
108543894  CERS5; ceramide synthase 5 [KO:K23727] [EC:2.3.1.291]
108542338  DEGS2; sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
108528244  DEGS1; sphingolipid delta(4)-desaturase DES1 isoform X1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
108543246  SMPD1; sphingomyelin phosphodiesterase [KO:K12350] [EC:3.1.4.12]
108527547  SGMS1; phosphatidylcholine:ceramide cholinephosphotransferase 1 isoform X1 [KO:K04714] [EC:2.7.8.27]
108515885  SGMS2; phosphatidylcholine:ceramide cholinephosphotransferase 2 [KO:K04714] [EC:2.7.8.27]
108523223  phosphatidylcholine:ceramide cholinephosphotransferase 1 [KO:K04714] [EC:2.7.8.27]
108520255  TNF; tumor necrosis factor isoform X1 [KO:K03156]
108536511  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
108529428  NSMAF; LOW QUALITY PROTEIN: protein FAN [KO:K18953]
108533803  SMPD2; sphingomyelin phosphodiesterase 2 [KO:K12351] [EC:3.1.4.12]
108526474  ASAH1; acid ceramidase [KO:K12348] [EC:3.5.1.23]
108527549  neutral ceramidase isoform X1 [KO:K12349] [EC:3.5.1.23]
108526237  ACER1; alkaline ceramidase 1 [KO:K01441] [EC:3.5.1.23]
108540842  ACER2; alkaline ceramidase 2 isoform X1 [KO:K01441] [EC:3.5.1.23]
108515408  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
108542901  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
108531312  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
108541711  BID; BH3-interacting domain death agonist [KO:K04726]
108523624  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
108522968  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
108537794  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
108521141  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
108517508  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
108528326  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
108528327  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
108539403  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
108539422  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
108536030  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
108512498  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108539069  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
108521880  AKT1; LOW QUALITY PROTEIN: RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108526412  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
108518653  PPP2CB; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
108529557  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
108536465  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
108523953  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
108537733  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform [KO:K04354]
108543389  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
108516076  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform-like [KO:K04354]
108538800  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
108529771  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
108512434  PPP2R3A; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha [KO:K11583]
108519463  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
108538576  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta-like [KO:K11583]
108542326  PPP2R5C; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform [KO:K11584]
108533479  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
108544296  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
108543026  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
108515863  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
108514363  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
108531905  FCER1A; high affinity immunoglobulin epsilon receptor subunit alpha [KO:K08089]
108541302  MS4A2; high affinity immunoglobulin epsilon receptor subunit beta [KO:K08090]
108521184  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
108512073  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
108543205  GAB2; GRB2-associated-binding protein 2 [KO:K08091]
108544591  PIK3CB; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
108532960  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
108539355  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108535636  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
108534276  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
108541175  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
108524801  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
108540404  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
108537441  SPHK1; sphingosine kinase 1 isoform X1 [KO:K04718] [EC:2.7.1.91]
108523630  SPHK2; sphingosine kinase 2 isoform X1 [KO:K04718] [EC:2.7.1.91]
108530457  KNG1; kininogen-1 isoform X1 [KO:K03898]
108514998  ADORA1; adenosine receptor A1 isoform X1 [KO:K04265]
108528084  adenosine receptor A3 isoform X1 [KO:K04268]
108519129  BDKRB2; LOW QUALITY PROTEIN: B2 bradykinin receptor [KO:K03916]
108530035  OPRD1; delta-type opioid receptor [KO:K04213]
108519632  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
108534866  GNAI1; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
108526962  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
108526885  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
108542252  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
108527553  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
108527564  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
108522504  PRKCE; protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
108523695  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
108536070  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
108542435  SGPP1; sphingosine-1-phosphate phosphatase 1 [KO:K04716] [EC:3.1.3.-]
108532648  SGPP2; sphingosine-1-phosphate phosphatase 2 [KO:K04717] [EC:3.1.3.-]
108529411  ABCC1; multidrug resistance-associated protein 1 isoform X1 [KO:K05665] [EC:7.6.2.3]
108516894  SGPL1; sphingosine-1-phosphate lyase 1 isoform X1 [KO:K01634] [EC:4.1.2.27]
108519966  S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288]
108534479  S1PR2; sphingosine 1-phosphate receptor 2 [KO:K04292]
108543525  HRAS; GTPase HRas isoform X1 [KO:K02833]
108523748  KRAS; GTPase KRas isoform X1 [KO:K07827]
108528122  NRAS; GTPase NRas [KO:K07828]
108517986  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
108514672  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
108512087  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
108532525  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
108523982  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
108515883  ras-related C3 botulinum toxin substrate 1-like isoform X1 [KO:K04392]
108512764  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
108534092  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
108532237  S1PR3; sphingosine 1-phosphate receptor 3 [KO:K04290]
108542641  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
108517746  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
108538857  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
108529452  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
108512681  S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293]
108539979  S1PR5; sphingosine 1-phosphate receptor 5 [KO:K04295]
108543875  GNA12; guanine nucleotide-binding protein subunit alpha-12 isoform X1 [KO:K04346]
108517753  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
108526989  RHOA; transforming protein RhoA [KO:K04513]
108530562  ROCK1; LOW QUALITY PROTEIN: rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
108516461  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
108527540  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]
108532817  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
108543519  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
rbb00600  Sphingolipid metabolism
rbb04010  MAPK signaling pathway
rbb04142  Lysosome
rbb04151  PI3K-Akt signaling pathway
KO pathway
ko04071   
LinkDB

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