KEGG   PATHWAY: psiu04071
Entry
psiu04071                   Pathway                                
Name
Sphingolipid signaling pathway - Phocoena sinus (vaquita)
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
psiu04071  Sphingolipid signaling pathway
psiu04071

Organism
Phocoena sinus (vaquita) [GN:psiu]
Gene
116748709  SPTLC2; serine palmitoyltransferase 2 isoform X1 [KO:K00654] [EC:2.3.1.50]
116755775  SPTLC1; serine palmitoyltransferase 1 [KO:K00654] [EC:2.3.1.50]
116739486  SPTLC3; serine palmitoyltransferase 3 isoform X1 [KO:K00654] [EC:2.3.1.50]
116749707  SPTSSA; serine palmitoyltransferase small subunit A [KO:K26384]
116752560  serine palmitoyltransferase small subunit B [KO:K26384]
116750406  CERS1; ceramide synthase 1 [KO:K04710] [EC:2.3.1.299]
116751347  CERS4; ceramide synthase 4 [KO:K24621] [EC:2.3.1.297]
116752069  CERS2; ceramide synthase 2 [KO:K24621] [EC:2.3.1.297]
116749338  CERS3; ceramide synthase 3 [KO:K24622] [EC:2.3.1.297 2.3.1.298]
116760255  CERS5; ceramide synthase 5 isoform X1 [KO:K23727] [EC:2.3.1.291]
116756288  CERS6; ceramide synthase 6 isoform X1 [KO:K23727] [EC:2.3.1.291]
116748468  DEGS2; sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
116757512  DEGS1; sphingolipid delta(4)-desaturase DES1 isoform X1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
116758540  SMPD1; sphingomyelin phosphodiesterase isoform X1 [KO:K12350] [EC:3.1.4.12]
116754399  SGMS2; phosphatidylcholine:ceramide cholinephosphotransferase 2 isoform X1 [KO:K04714] [EC:2.7.8.27]
116741663  SGMS1; phosphatidylcholine:ceramide cholinephosphotransferase 1 [KO:K04714] [EC:2.7.8.27]
116762489  TNF; tumor necrosis factor [KO:K03156]
116760562  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
116742173  NSMAF; LOW QUALITY PROTEIN: protein FAN [KO:K18953]
116763524  SMPD2; sphingomyelin phosphodiesterase 2 [KO:K12351] [EC:3.1.4.12]
116746719  ASAH1; acid ceramidase isoform X1 [KO:K12348] [EC:3.5.1.23]
116742049  ASAH2; neutral ceramidase isoform X1 [KO:K12349] [EC:3.5.1.23]
116756125  ACER2; alkaline ceramidase 2 [KO:K01441] [EC:3.5.1.23]
116752318  ACER1; alkaline ceramidase 1 [KO:K01441] [EC:3.5.1.23]
116755387  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
116758017  CTSD; cathepsin D isoform X1 [KO:K01379] [EC:3.4.23.5]
116761091  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
116744670  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
116763459  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
116754735  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116741257  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
116751302  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
116760605  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
116760782  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
116762796  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
116762798  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
116752778  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
116743673  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116759669  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116748950  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116738931  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
116746674  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
116750919  PPP2CA; serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform [KO:K04382] [EC:3.1.3.16]
116743774  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform isoform X1 [KO:K03456]
116757415  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
116746197  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform-like [KO:K04354]
116754762  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
116755706  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
116741434  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
116752026  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
116753268  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha [KO:K11583]
116747993  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
116748480  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
116746995  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
116761517  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform isoform X1 [KO:K11584]
116748702  PPP2R5E; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform [KO:K11584]
116751199  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
116758459  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
116745739  TP53; cellular tumor antigen p53 [KO:K04451]
116759518  FCER1A; high affinity immunoglobulin epsilon receptor subunit alpha isoform X1 [KO:K08089]
116758492  high affinity immunoglobulin epsilon receptor subunit beta-like [KO:K08090]
116754885  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
116763801  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
116757591  GAB2; GRB2-associated-binding protein 2 [KO:K08091]
116752953  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116752990  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
116751286  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116750604  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
116742613  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
116751944  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
116746315  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
116753650  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
116746005  SPHK1; sphingosine kinase 1 isoform X1 [KO:K04718] [EC:2.7.1.91]
116743941  SPHK2; sphingosine kinase 2 isoform X1 [KO:K04718] [EC:2.7.1.91]
116753679  KNG1; kininogen-1 isoform X1 [KO:K03898]
116741695  ADORA1; adenosine receptor A1 [KO:K04265]
116746141  BDKRB2; B2 bradykinin receptor [KO:K03916]
116758988  OPRD1; delta-type opioid receptor [KO:K04213]
116761812  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
116749946  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
116759318  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
116749106  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
116740640  PLCB1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
116740954  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 [KO:K05858] [EC:3.1.4.11]
116758215  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
116764149  PRKCE; protein kinase C epsilon type isoform X1 [KO:K18050] [EC:2.7.11.13]
116738910  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116740620  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
116749890  SGPP1; sphingosine-1-phosphate phosphatase 1 [KO:K04716] [EC:3.1.3.-]
116756572  SGPP2; sphingosine-1-phosphate phosphatase 2 [KO:K04717] [EC:3.1.3.-]
116739899  ABCC1; multidrug resistance-associated protein 1 isoform X1 [KO:K05665] [EC:7.6.2.3]
116741252  SGPL1; sphingosine-1-phosphate lyase 1 [KO:K01634] [EC:4.1.2.27]
116763398  S1PR1; sphingosine 1-phosphate receptor 1 isoform X1 [KO:K04288]
116752242  S1PR2; sphingosine 1-phosphate receptor 2 [KO:K04292]
116757893  HRAS; GTPase HRas isoform X1 [KO:K02833]
116751649  uncharacterized protein LOC116751649 [KO:K02833]
116760326  KRAS; GTPase KRas isoform X1 [KO:K07827]
116739088  NRAS; GTPase NRas [KO:K07828]
116761625  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
116747589  MAP2K1; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116751189  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116739722  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
116759107  NOS3; LOW QUALITY PROTEIN: nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
116761737  LOW QUALITY PROTEIN: ras-related C3 botulinum toxin substrate 1-like [KO:K04392]
116739565  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
116760236  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
116745822  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
116756029  S1PR3; sphingosine 1-phosphate receptor 3 isoform X1 [KO:K04290]
116755414  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
116745476  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
116739537  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
116743766  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
116751181  S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293]
116751264  S1PR5; sphingosine 1-phosphate receptor 5 [KO:K04295]
116739840  GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
116745371  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
116762804  RHOA; transforming protein RhoA isoform X1 [KO:K04513]
116765160  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
116764174  ROCK2; rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.1]
116741761  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]
116754222  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
116758150  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
psiu00600  Sphingolipid metabolism
psiu04010  MAPK signaling pathway
psiu04142  Lysosome
psiu04151  PI3K-Akt signaling pathway
KO pathway
ko04071   
LinkDB

DBGET integrated database retrieval system