KEGG   PATHWAY: caty04071
Entry
caty04071                   Pathway                                
Name
Sphingolipid signaling pathway - Cercocebus atys (sooty mangabey)
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
caty04071  Sphingolipid signaling pathway
caty04071

Organism
Cercocebus atys (sooty mangabey) [GN:caty]
Gene
105578733  SPTLC1; serine palmitoyltransferase 1 isoform X1 [KO:K00654] [EC:2.3.1.50]
105582072  SPTLC3; serine palmitoyltransferase 3 isoform X1 [KO:K00654] [EC:2.3.1.50]
105590905  SPTLC2; serine palmitoyltransferase 2 [KO:K00654] [EC:2.3.1.50]
105592242  SPTSSA; serine palmitoyltransferase small subunit A [KO:K26384]
105571925  SPTSSB; serine palmitoyltransferase small subunit B [KO:K26384]
105571322  CERS1; LOW QUALITY PROTEIN: ceramide synthase 1 [KO:K04710] [EC:2.3.1.299]
105589123  CERS4; ceramide synthase 4 isoform X1 [KO:K24621] [EC:2.3.1.297]
105590207  CERS2; ceramide synthase 2 [KO:K24621] [EC:2.3.1.297]
105593986  CERS3; ceramide synthase 3 [KO:K24622] [EC:2.3.1.297 2.3.1.298]
105580163  CERS6; ceramide synthase 6 [KO:K23727] [EC:2.3.1.291]
105580356  CERS5; ceramide synthase 5 isoform X1 [KO:K23727] [EC:2.3.1.291]
105576085  ceramide synthase 6 [KO:K23727] [EC:2.3.1.291]
105576957  DEGS1; sphingolipid delta(4)-desaturase DES1 isoform X1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
105596688  DEGS2; sphingolipid delta(4)-desaturase/C4-hydroxylase DES2 isoform X1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
105575054  SMPD1; sphingomyelin phosphodiesterase [KO:K12350] [EC:3.1.4.12]
105587181  SGMS1; phosphatidylcholine:ceramide cholinephosphotransferase 1 [KO:K04714] [EC:2.7.8.27]
105571409  SGMS2; phosphatidylcholine:ceramide cholinephosphotransferase 2 [KO:K04714] [EC:2.7.8.27]
105573465  TNF; tumor necrosis factor [KO:K03156]
105583011  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
105600598  NSMAF; protein FAN isoform X1 [KO:K18953]
105581356  SMPD2; sphingomyelin phosphodiesterase 2 isoform X1 [KO:K12351] [EC:3.1.4.12]
105601404  ASAH1; acid ceramidase [KO:K12348] [EC:3.5.1.23]
105587184  ASAH2; neutral ceramidase [KO:K12349] [EC:3.5.1.23]
105584299  ACER2; alkaline ceramidase 2 [KO:K01441] [EC:3.5.1.23]
105591853  ACER1; alkaline ceramidase 1 isoform X1 [KO:K01441] [EC:3.5.1.23]
105587262  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
105580591  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
105577246  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
105591256  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
105595265  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
105600400  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
105590417  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
105591436  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
105576775  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
105592690  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
105592727  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
105586882  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
105586884  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
105594441  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
105596769  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105597977  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105574942  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
105590006  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
105579128  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
105599769  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
105595396  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
105588701  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
105599971  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
105585423  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
105579187  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
105599017  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
105586412  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
105589065  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
105590313  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
105577041  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
105577467  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
105596715  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
105582812  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
105591568  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
105582225  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
105601252  FCER1A; high affinity immunoglobulin epsilon receptor subunit alpha isoform X1 [KO:K08089]
105573016  MS4A2; high affinity immunoglobulin epsilon receptor subunit beta [KO:K08090]
105589248  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma isoform X1 [KO:K07983]
105581387  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
105578686  GAB2; GRB2-associated-binding protein 2 isoform X1 [KO:K08091]
105586383  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105580892  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
105597716  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105571321  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
105594576  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
105599262  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
105586073  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
105583465  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
105577691  SPHK1; sphingosine kinase 1 isoform X1 [KO:K04718] [EC:2.7.1.91]
105595245  SPHK2; sphingosine kinase 2 isoform X1 [KO:K04718] [EC:2.7.1.91]
105575221  KNG1; kininogen-1 isoform X1 [KO:K03898]
105575750  ADORA1; adenosine receptor A1 [KO:K04265]
105596655  BDKRB2; B2 bradykinin receptor [KO:K03916]
105594868  OPRD1; delta-type opioid receptor [KO:K04213]
105594342  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
105573715  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
105583233  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
105577494  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
105574260  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
105582089  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
105582092  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
105590592  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
105598233  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
105598850  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
105582818  SGPP1; sphingosine-1-phosphate phosphatase 1 [KO:K04716] [EC:3.1.3.-]
105587000  SGPP2; sphingosine-1-phosphate phosphatase 2 [KO:K04717] [EC:3.1.3.-]
105572213  ABCC1; multidrug resistance-associated protein 1 isoform X1 [KO:K05665] [EC:7.6.2.3]
105597461  SGPL1; sphingosine-1-phosphate lyase 1 [KO:K01634] [EC:4.1.2.27]
105590129  S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288]
105571281  S1PR2; LOW QUALITY PROTEIN: sphingosine 1-phosphate receptor 2 [KO:K04292]
105577198  HRAS; GTPase HRas isoform X1 [KO:K02833]
105585038  KRAS; GTPase KRas isoform X1 [KO:K07827]
105596344  NRAS; GTPase NRas isoform X1 [KO:K07828]
105585803  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
105601165  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
105591800  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
105573290  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
105584734  NOS3; nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
105584356  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
105575821  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
105588572  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
105584276  S1PR3; sphingosine 1-phosphate receptor 3 [KO:K04290]
105584209  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
105599331  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
105586076  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
105595654  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
105591771  S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293]
105601448  S1PR5; sphingosine 1-phosphate receptor 5 [KO:K04295]
105571739  GNA12; guanine nucleotide-binding protein subunit alpha-12 isoform X1 [KO:K04346]
105573047  GNA13; guanine nucleotide-binding protein subunit alpha-13 isoform X1 [KO:K04639]
105573691  RHOA; transforming protein RhoA [KO:K04513]
105583987  ROCK1; rho-associated protein kinase 1 [KO:K04514] [EC:2.7.11.1]
105578625  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
105587171  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]
105571369  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
105577432  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
caty00600  Sphingolipid metabolism
caty04010  MAPK signaling pathway
caty04142  Lysosome
caty04151  PI3K-Akt signaling pathway
KO pathway
ko04071   
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