KEGG   PATHWAY: ggo04071
Entry
ggo04071                    Pathway                                
Name
Sphingolipid signaling pathway - Gorilla gorilla gorilla (western lowland gorilla)
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
ggo04071  Sphingolipid signaling pathway
ggo04071

Organism
Gorilla gorilla gorilla (western lowland gorilla) [GN:ggo]
Gene
101148765  SPTLC2; serine palmitoyltransferase 2 [KO:K00654] [EC:2.3.1.50]
101135062  SPTLC3; serine palmitoyltransferase 3 isoform X1 [KO:K00654] [EC:2.3.1.50]
101145241  SPTLC1; serine palmitoyltransferase 1 isoform X1 [KO:K00654] [EC:2.3.1.50]
115930601  SPTSSA; serine palmitoyltransferase small subunit A [KO:K26384]
101131314  SPTSSB; serine palmitoyltransferase small subunit B [KO:K26384]
109024075  CERS1; ceramide synthase 1 isoform X2 [KO:K04710] [EC:2.3.1.299]
101148109  CERS2; ceramide synthase 2 [KO:K24621] [EC:2.3.1.297]
101128445  CERS3; ceramide synthase 3 [KO:K24622] [EC:2.3.1.297 2.3.1.298]
101126713  CERS6; ceramide synthase 6 isoform X1 [KO:K23727] [EC:2.3.1.291]
101143812  DEGS2; sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
101151016  DEGS1; sphingolipid delta(4)-desaturase DES1 isoform X1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
101145253  SMPD1; sphingomyelin phosphodiesterase isoform X1 [KO:K12350] [EC:3.1.4.12]
101138449  SGMS2; phosphatidylcholine:ceramide cholinephosphotransferase 2 [KO:K04714] [EC:2.7.8.27]
101138874  SGMS1; phosphatidylcholine:ceramide cholinephosphotransferase 1 isoform X1 [KO:K04714] [EC:2.7.8.27]
101149216  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
101135083  NSMAF; protein FAN isoform X1 [KO:K18953]
101128835  SMPD2; sphingomyelin phosphodiesterase 2 [KO:K12351] [EC:3.1.4.12]
101149522  ASAH1; acid ceramidase isoform X1 [KO:K12348] [EC:3.5.1.23]
101146782  neutral ceramidase isoform X2 [KO:K12349] [EC:3.5.1.23]
101131822  ACER1; alkaline ceramidase 1 [KO:K01441] [EC:3.5.1.23]
101133313  ACER2; alkaline ceramidase 2 isoform X1 [KO:K01441] [EC:3.5.1.23]
101139980  LOW QUALITY PROTEIN: alkaline ceramidase 2-like [KO:K01441] [EC:3.5.1.23]
101146975  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
101144745  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
101142032  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
101152769  BAX; apoptosis regulator BAX isoform X3 [KO:K02159]
101147354  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X2 [KO:K04426] [EC:2.7.11.25]
101152026  MAPK9; mitogen-activated protein kinase 9 isoform X4 [KO:K04440] [EC:2.7.11.24]
101124033  MAPK8; mitogen-activated protein kinase 8 isoform X4 [KO:K04440] [EC:2.7.11.24]
101133141  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
101134492  MAPK12; mitogen-activated protein kinase 12 isoform X2 [KO:K04441] [EC:2.7.11.24]
101134843  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
101148438  MAPK13; mitogen-activated protein kinase 13 isoform X3 [KO:K04441] [EC:2.7.11.24]
101152640  MAPK14; mitogen-activated protein kinase 14 isoform X2 [KO:K04441] [EC:2.7.11.24]
101127296  PRKCZ; protein kinase C zeta type isoform X2 [KO:K18952] [EC:2.7.11.13]
101137723  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
101138019  AKT3; RAC-gamma serine/threonine-protein kinase isoform X2 [KO:K04456] [EC:2.7.11.1]
101136123  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
101125226  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
101152519  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
101142397  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
101145146  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
101140471  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X3 [KO:K04354]
101129571  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
101132841  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
101135043  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X7 [KO:K04354]
101127833  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
101147502  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
101134784  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X4 [KO:K11583]
115930163  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta-like isoform X1 [KO:K11583]
115932828  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta-like isoform X1 [KO:K11583]
101127596  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X8 [KO:K11584]
101131887  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
101134228  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
101143530  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform isoform X1 [KO:K11584]
109024753  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform-like [KO:K11584]
101133524  TP53; cellular tumor antigen p53 isoform X2 [KO:K04451]
101126100  FCER1A; high affinity immunoglobulin epsilon receptor subunit alpha [KO:K08089]
101139625  MS4A2; high affinity immunoglobulin epsilon receptor subunit beta isoform X1 [KO:K08090]
101125858  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
101143006  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
101148004  GAB2; GRB2-associated-binding protein 2 isoform X1 [KO:K08091]
101143811  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101146434  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
101152123  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101130978  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
101135298  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101129336  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
101135150  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
101135996  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
101127850  SPHK1; sphingosine kinase 1 isoform X1 [KO:K04718] [EC:2.7.1.91]
101138554  KNG1; kininogen-1 isoform X1 [KO:K03898]
101140567  ADORA1; adenosine receptor A1 isoform X1 [KO:K04265]
101127788  adenosine receptor A3 isoform X3 [KO:K04268]
101132514  BDKRB2; B2 bradykinin receptor isoform X1 [KO:K03916]
101125616  GNAI3; guanine nucleotide-binding protein G(I) subunit alpha-3 [KO:K04630]
101154597  GNAI1; guanine nucleotide-binding protein G(I) subunit alpha-1 isoform X1 [KO:K04630]
101140350  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X4 [KO:K05858] [EC:3.1.4.11]
101153613  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
101129357  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform X1 [KO:K05858] [EC:3.1.4.11]
101154323  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X2 [KO:K05858] [EC:3.1.4.11]
101133595  PRKCE; protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
101140164  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101135988  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101140990  SGPP1; sphingosine-1-phosphate phosphatase 1 [KO:K04716] [EC:3.1.3.-]
101154040  SGPP2; sphingosine-1-phosphate phosphatase 2 [KO:K04717] [EC:3.1.3.-]
101144014  SGPL1; sphingosine-1-phosphate lyase 1 isoform X1 [KO:K01634] [EC:4.1.2.27]
101127904  S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288]
101136425  HRAS; GTPase HRas isoform X1 [KO:K02833]
101144039  KRAS; GTPase KRas isoform X2 [KO:K07827]
101146562  NRAS; GTPase NRas [KO:K07828]
101136454  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X3 [KO:K04366] [EC:2.7.11.1]
101132391  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101126885  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101147096  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
101147811  LOW QUALITY PROTEIN: putative 3-phosphoinositide-dependent protein kinase 2 [KO:K06276] [EC:2.7.11.1]
101128007  NOS3; nitric oxide synthase 3 isoform X1 [KO:K13242] [EC:1.14.13.39]
101135430  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X3 [KO:K04392]
101141534  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
101127776  S1PR3; sphingosine 1-phosphate receptor 3 [KO:K04290]
101149651  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
101124828  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
101150691  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101139074  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
101150342  S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293]
101147243  GNA12; guanine nucleotide-binding protein subunit alpha-12 isoform X1 [KO:K04346]
101152866  GNA13; guanine nucleotide-binding protein subunit alpha-13 isoform X1 [KO:K04639]
101134778  RHOA; transforming protein RhoA [KO:K04513]
101154194  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
101134988  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
101147526  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]
134756931  LOW QUALITY PROTEIN: phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN-like [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
101153465  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101150285  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
ggo00600  Sphingolipid metabolism
ggo04010  MAPK signaling pathway
ggo04142  Lysosome
ggo04151  PI3K-Akt signaling pathway
KO pathway
ko04071   
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