KEGG   PATHWAY: shon04071
Entry
shon04071                   Pathway                                
Name
Sphingolipid signaling pathway - Sturnira hondurensis
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
shon04071  Sphingolipid signaling pathway
shon04071

Organism
Sturnira hondurensis [GN:shon]
Gene
118983698  SPTLC1; serine palmitoyltransferase 1 [KO:K00654] [EC:2.3.1.50]
118976585  SPTLC2; serine palmitoyltransferase 2 [KO:K00654] [EC:2.3.1.50]
118976732  SPTLC3; serine palmitoyltransferase 3 [KO:K00654] [EC:2.3.1.50]
118989912  SPTSSA; serine palmitoyltransferase small subunit A [KO:K26384]
118987438  SPTSSB; serine palmitoyltransferase small subunit B [KO:K26384]
118975143  CERS1; ceramide synthase 1 [KO:K04710] [EC:2.3.1.299]
118994065  CERS4; ceramide synthase 4 [KO:K24621] [EC:2.3.1.297]
118992022  CERS3; ceramide synthase 3 [KO:K24622] [EC:2.3.1.297 2.3.1.298]
118976441  CERS5; ceramide synthase 5 isoform X1 [KO:K23727] [EC:2.3.1.291]
118985744  CERS6; ceramide synthase 6 isoform X1 [KO:K23727] [EC:2.3.1.291]
118976942  DEGS2; sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 isoform X1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
119003264  DEGS1; sphingolipid delta(4)-desaturase DES1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
118990805  SMPD1; sphingomyelin phosphodiesterase [KO:K12350] [EC:3.1.4.12]
118977086  SGMS2; phosphatidylcholine:ceramide cholinephosphotransferase 2 [KO:K04714] [EC:2.7.8.27]
119001528  SGMS1; phosphatidylcholine:ceramide cholinephosphotransferase 1 [KO:K04714] [EC:2.7.8.27]
118987585  TNF; tumor necrosis factor isoform X1 [KO:K03156]
119002559  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A isoform X1 [KO:K03158]
118974984  NSMAF; protein FAN isoform X1 [KO:K18953]
119000162  SMPD2; sphingomyelin phosphodiesterase 2 [KO:K12351] [EC:3.1.4.12]
118993101  ASAH1; acid ceramidase [KO:K12348] [EC:3.5.1.23]
119001520  ASAH2; neutral ceramidase [KO:K12349] [EC:3.5.1.23]
118998002  ACER2; alkaline ceramidase 2 [KO:K01441] [EC:3.5.1.23]
118984599  ACER1; alkaline ceramidase 1 [KO:K01441] [EC:3.5.1.23]
118983883  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein isoform X1 [KO:K03171]
118980132  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
118988338  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
118995133  BID; BH3-interacting domain death agonist [KO:K04726]
118986673  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
118976281  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
118994117  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
118995102  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
118988883  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
118988898  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
118998971  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
118998973  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
118998179  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
118988441  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
119003271  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
118988089  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
118979386  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
118990083  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
118993143  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
118999829  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
119000517  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
118981873  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
118990570  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
118986187  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
118987064  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma [KO:K04354]
118997544  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
118974330  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
118993935  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
118974181  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
118991634  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
118991697  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
118976816  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
118976955  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
118974748  TP53; cellular tumor antigen p53 [KO:K04451]
118996404  FCER1A; high affinity immunoglobulin epsilon receptor subunit alpha [KO:K08089]
118996859  MS4A2; high affinity immunoglobulin epsilon receptor subunit beta [KO:K08090]
118979098  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
119000185  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
118997522  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118986375  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
118995662  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
118982454  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
118975178  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
118998595  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
119001060  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
118987399  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
119000132  SPHK1; sphingosine kinase 1 isoform X1 [KO:K04718] [EC:2.7.1.91]
118983148  KNG1; kininogen-1 [KO:K03898]
119003903  ADORA1; adenosine receptor A1 [KO:K04265]
118982001  ADORA3; adenosine receptor A3 [KO:K04268]
118976804  BDKRB2; B2 bradykinin receptor isoform X1 [KO:K03916]
118994524  OPRD1; delta-type opioid receptor isoform X1 [KO:K04213]
118989455  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
118990034  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
119000994  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
118990867  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
118990869  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
118991671  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
118993594  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 [KO:K05858] [EC:3.1.4.11]
119001241  PRKCE; protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
119000423  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
119001903  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
118976591  SGPP1; sphingosine-1-phosphate phosphatase 1 isoform X1 [KO:K04716] [EC:3.1.3.-]
118975362  SGPP2; sphingosine-1-phosphate phosphatase 2 [KO:K04717] [EC:3.1.3.-]
119001997  ABCC1; multidrug resistance-associated protein 1 [KO:K05665] [EC:7.6.2.3]
118993444  SGPL1; sphingosine-1-phosphate lyase 1 [KO:K01634] [EC:4.1.2.27]
118990625  S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288]
118982230  HRAS; GTPase HRas isoform X1 [KO:K02833]
118978497  KRAS; GTPase KRas isoform X1 [KO:K07827]
118981977  NRAS; GTPase NRas [KO:K07828]
118990300  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
118992336  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
118984505  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
118985111  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
118975507  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
118995001  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
119002327  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
119002854  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
118993732  S1PR3; sphingosine 1-phosphate receptor 3 [KO:K04290]
118976055  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
119003729  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
119004000  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
118986634  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
118984475  S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293]
118995031  GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
119003776  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
118989480  RHOA; transforming protein RhoA [KO:K04513]
118976915  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
118988767  ROCK2; rho-associated protein kinase 2 isoform X1 [KO:K17388] [EC:2.7.11.1]
118988011  PTEN; phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
118979949  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
118991736  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
shon00600  Sphingolipid metabolism
shon04010  MAPK signaling pathway
shon04142  Lysosome
shon04151  PI3K-Akt signaling pathway
KO pathway
ko04071   
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