KEGG   PATHWAY: nvs04071
Entry
nvs04071                    Pathway                                
Name
Sphingolipid signaling pathway - Neogale vison (American mink)
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
nvs04071  Sphingolipid signaling pathway
nvs04071

Organism
Neogale vison (American mink) [GN:nvs]
Gene
122905386  LOW QUALITY PROTEIN: serine palmitoyltransferase 1-like [KO:K00654] [EC:2.3.1.50]
122893976  SPTLC2; serine palmitoyltransferase 2 [KO:K00654] [EC:2.3.1.50]
122916267  SPTLC3; serine palmitoyltransferase 3 [KO:K00654] [EC:2.3.1.50]
122917808  SPTLC1; serine palmitoyltransferase 1 [KO:K00654] [EC:2.3.1.50]
122908663  serine palmitoyltransferase small subunit B [KO:K26384]
122894699  SPTSSA; serine palmitoyltransferase small subunit A [KO:K26384]
122909567  CERS1; ceramide synthase 1 [KO:K04710] [EC:2.3.1.299]
122900484  CERS2; ceramide synthase 2 [KO:K24621] [EC:2.3.1.297]
122909799  CERS4; ceramide synthase 4 isoform X1 [KO:K24621] [EC:2.3.1.297]
122893869  CERS3; ceramide synthase 3 [KO:K24622] [EC:2.3.1.297 2.3.1.298]
122891487  CERS5; ceramide synthase 5 isoform X1 [KO:K23727] [EC:2.3.1.291]
122902562  CERS6; ceramide synthase 6 isoform X1 [KO:K23727] [EC:2.3.1.291]
122918701  DEGS1; sphingolipid delta(4)-desaturase DES1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
122892985  DEGS2; sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
122912672  SMPD1; sphingomyelin phosphodiesterase [KO:K12350] [EC:3.1.4.12]
122889285  SGMS2; phosphatidylcholine:ceramide cholinephosphotransferase 2 [KO:K04714] [EC:2.7.8.27]
122900673  SGMS1; phosphatidylcholine:ceramide cholinephosphotransferase 1 isoform X1 [KO:K04714] [EC:2.7.8.27]
122899945  TNF; tumor necrosis factor isoform X1 [KO:K03156]
122892505  TNFRSF1A; tumor necrosis factor receptor superfamily member 1A [KO:K03158]
122904576  NSMAF; protein FAN isoform X1 [KO:K18953]
122903822  SMPD2; sphingomyelin phosphodiesterase 2 [KO:K12351] [EC:3.1.4.12]
122889922  ASAH1; acid ceramidase [KO:K12348] [EC:3.5.1.23]
122900676  ASAH2; neutral ceramidase isoform X1 [KO:K12349] [EC:3.5.1.23]
122909827  ACER1; alkaline ceramidase 1 [KO:K01441] [EC:3.5.1.23]
122917572  ACER2; alkaline ceramidase 2 isoform X1 [KO:K01441] [EC:3.5.1.23]
122911363  TRADD; tumor necrosis factor receptor type 1-associated DEATH domain protein [KO:K03171]
122917083  TRAF2; TNF receptor-associated factor 2 isoform X1 [KO:K03173] [EC:2.3.2.27]
122913243  CTSD; cathepsin D [KO:K01379] [EC:3.4.23.5]
122889094  BH3-interacting domain death agonist-like [KO:K04726]
122891540  BID; BH3-interacting domain death agonist [KO:K04726]
122911843  BAX; apoptosis regulator BAX [KO:K02159]
122906270  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
122889452  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
122900866  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
122915651  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
122891909  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
122891975  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
122910068  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
122910086  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
122899350  PRKCZ; protein kinase C zeta type isoform X1 [KO:K18952] [EC:2.7.11.13]
122918524  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122912036  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
122894172  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
122902835  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
122889911  PPP2CB; serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
122891679  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
122911710  PPP2R1A; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
122912265  PPP2R1B; serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
122889649  PPP2R2B; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform isoform X1 [KO:K04354]
122889741  PPP2R2A; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
122890558  PPP2R2C; protein phosphatase 2, regulatory subunit B, gamma isoform X1 [KO:K04354]
122901225  PPP2R2D; serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform isoform X1 [KO:K04354]
122908920  PPP2R3A; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
122894083  PPP2R3C; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma [KO:K11583]
122896293  PPP2R3B; serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta isoform X1 [KO:K11583]
122918553  PPP2R5A; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
122913079  PPP2R5B; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform [KO:K11584]
122908357  PPP2R5D; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
122893443  PPP2R5C; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
122893946  PPP2R5E; serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
122906719  TP53; cellular tumor antigen p53 [KO:K04451]
122918055  FCER1A; LOW QUALITY PROTEIN: high affinity immunoglobulin epsilon receptor subunit alpha [KO:K08089]
122913683  high affinity immunoglobulin epsilon receptor subunit beta-like [KO:K08090]
122914525  high affinity immunoglobulin epsilon receptor subunit beta-like [KO:K08090]
122914527  LOW QUALITY PROTEIN: high affinity immunoglobulin epsilon receptor subunit beta-like [KO:K08090]
122914530  high affinity immunoglobulin epsilon receptor subunit beta-like isoform X1 [KO:K08090]
122918079  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
122903454  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
122912543  GAB2; GRB2-associated-binding protein 2 isoform X1 [KO:K08091]
122899425  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
122908712  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
122908899  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
122918946  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
122899916  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
122909588  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
122906672  PLD2; phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
122908696  PLD1; phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
122911860  SPHK2; sphingosine kinase 2 isoform X1 [KO:K04718] [EC:2.7.1.91]
122905958  SPHK1; sphingosine kinase 1 isoform X1 [KO:K04718] [EC:2.7.1.91]
122908785  KNG1; kininogen-1 isoform X1 [KO:K03898]
122918809  ADORA1; adenosine receptor A1 [KO:K04265]
122898801  ADORA3; adenosine receptor A3 [KO:K04268]
122893102  BDKRB2; B2 bradykinin receptor isoform X1 [KO:K03916]
122898631  OPRD1; delta-type opioid receptor [KO:K04213]
122904758  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
122900295  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
122909406  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
122913059  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
122916255  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X1 [KO:K05858] [EC:3.1.4.11]
122916256  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
122916358  PRKCE; protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
122895342  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
122903200  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
122892886  SGPP1; sphingosine-1-phosphate phosphatase 1 [KO:K04716] [EC:3.1.3.-]
122902353  SGPP2; sphingosine-1-phosphate phosphatase 2 [KO:K04717] [EC:3.1.3.-]
122895586  ABCC1; multidrug resistance-associated protein 1 [KO:K05665] [EC:7.6.2.3]
122900762  SGPL1; sphingosine-1-phosphate lyase 1 [KO:K01634] [EC:4.1.2.27]
122900251  S1PR1; sphingosine 1-phosphate receptor 1 [KO:K04288]
122909745  S1PR2; sphingosine 1-phosphate receptor 2 [KO:K04292]
122913220  HRAS; GTPase HRas isoform X1 [KO:K02833]
122892446  KRAS; GTPase KRas isoform X1 [KO:K07827]
122899136  LOW QUALITY PROTEIN: GTPase NRas-like [KO:K07828]
122900359  NRAS; GTPase NRas [KO:K07828]
122909192  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
122892965  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
122909871  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
122895932  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
122905198  NOS3; nitric oxide synthase, endothelial [KO:K13242] [EC:1.14.13.39]
122895963  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
122891553  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
122905874  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
122916991  S1PR3; sphingosine 1-phosphate receptor 3 [KO:K04290]
122917675  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
122906063  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
122895627  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
122911685  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
122910826  S1PR4; sphingosine 1-phosphate receptor 4 [KO:K04293]
122909730  S1PR5; sphingosine 1-phosphate receptor 5 [KO:K04295]
122896083  GNA12; guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
122906056  GNA13; guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
122909429  RHOA; transforming protein RhoA [KO:K04513]
122902995  ROCK1; rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
122915310  ROCK2; rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.1]
122900668  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]
122889330  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
122913121  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
nvs00600  Sphingolipid metabolism
nvs04010  MAPK signaling pathway
nvs04142  Lysosome
nvs04151  PI3K-Akt signaling pathway
KO pathway
ko04071   
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