KEGG   PATHWAY: ptg04071
Entry
ptg04071                    Pathway                                
Name
Sphingolipid signaling pathway - Panthera tigris altaica (Amur tiger)
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
ptg04071  Sphingolipid signaling pathway
ptg04071

Organism
Panthera tigris altaica (Amur tiger) [GN:ptg]
Gene
102948661  [KO:K08090]
102948771  CERS6; ceramide synthase 6 [KO:K23727]
102949153  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
102949460  PPP2R5E; protein phosphatase 2 regulatory subunit B'epsilon [KO:K11584]
102949853  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102949872  PPP2R2D; protein phosphatase 2 regulatory subunit Bdelta [KO:K04354]
102949986  ROCK2; Rho associated coiled-coil containing protein kinase 2 [KO:K17388] [EC:2.7.11.39]
102950183  NSMAF; neutral sphingomyelinase activation associated factor [KO:K18953]
102950880  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
102951047  PPP2R5A; protein phosphatase 2 regulatory subunit B'alpha [KO:K11584]
102951132  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
102951141  PPP2R1A; protein phosphatase 2 scaffold subunit Aalpha [KO:K03456]
102951159  GNAI3; G protein subunit alpha i3 [KO:K04630]
102951165  SGPL1; sphingosine-1-phosphate lyase 1 [KO:K01634] [EC:4.1.2.27]
102951261  PPP2R2B; protein phosphatase 2 regulatory subunit Bbeta [KO:K04354]
102951809  BID; BH3 interacting domain death agonist [KO:K04726]
102952119  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102952197  PPP2R5B; protein phosphatase 2 regulatory subunit B'beta [KO:K11584]
102952555  RHOA; ras homolog family member A [KO:K04513]
102952603  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102952814  PRKCB; protein kinase C beta [KO:K19662] [EC:2.7.11.13]
102952971  PPP2R2A; protein phosphatase 2 regulatory subunit Balpha [KO:K04354]
102952980  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102952993  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102953082  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102953263  ACER1; alkaline ceramidase 1 [KO:K01441] [EC:3.5.1.23]
102953487  BCL2; BCL2, apoptosis regulator [KO:K02161]
102954008  PPP2CA; protein phosphatase 2 catalytic subunit alpha [KO:K04382] [EC:3.1.3.16]
102954227  GNAQ; G protein subunit alpha q [KO:K04634]
102954501  GNAI1; G protein subunit alpha i1 [KO:K04630]
102954668  ADORA1; adenosine A1 receptor [KO:K04265]
102954757  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102954989  PPP2R5C; protein phosphatase 2 regulatory subunit B'gamma [KO:K11584]
102955504  RAC3; ras-related C3 botulinum toxin substrate 3 (rho family, small GTP binding protein Rac3) [KO:K07861]
102955852  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102956260  FYN; FYN proto-oncogene, Src family tyrosine kinase [KO:K05703] [EC:2.7.10.2]
102956451  PRKCE; protein kinase C epsilon [KO:K18050] [EC:2.7.11.13]
102956490  PRKCG; protein kinase C gamma [KO:K19663] [EC:2.7.11.13]
102956705  PPP2R3C; protein phosphatase 2 regulatory subunit B''gamma [KO:K11583]
102956714  S1PR1; sphingosine-1-phosphate receptor 1 [KO:K04288]
102956715  PPP2CB; protein phosphatase 2 catalytic subunit beta [KO:K04382] [EC:3.1.3.16]
102956747  ASAH2; N-acylsphingosine amidohydrolase 2 [KO:K12349] [EC:3.5.1.23]
102956793  TNFRSF1A; TNF receptor superfamily member 1A [KO:K03158]
102956808  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102956963  SPTLC3; serine palmitoyltransferase long chain base subunit 3 [KO:K00654] [EC:2.3.1.50]
102957023  SGMS1; sphingomyelin synthase 1 [KO:K04714] [EC:2.7.8.27 2.7.8.48 3.1.4.62]
102957170  SPTLC2; serine palmitoyltransferase long chain base subunit 2 [KO:K00654] [EC:2.3.1.50]
102957301  ORMDL2; ORMDL sphingolipid biosynthesis regulator 2 [KO:K28680]
102957350  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102958919  TNF; tumor necrosis factor [KO:K03156]
102959159  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102959485  PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
102959589  PPP2R5D; protein phosphatase 2 regulatory subunit B'delta [KO:K11584]
102960306  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102960317  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
102960424  PDPK1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
102960457  SPTLC1; serine palmitoyltransferase long chain base subunit 1 [KO:K00654] [EC:2.3.1.50]
102960528  KNG1; kininogen 1 [KO:K03898]
102960590  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102960646  PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
102960685  [KO:K18952] [EC:2.7.11.13]
102960964  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102960973  [KO:K18952] [EC:2.7.11.13]
102961052  GNA12; G protein subunit alpha 12 [KO:K04346]
102961054  BDKRB2; bradykinin receptor B2 [KO:K03916]
102961121  PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
102961190  S1PR2; sphingosine-1-phosphate receptor 2 [KO:K04292]
102961325  S1PR3; sphingosine-1-phosphate receptor 3 [KO:K04290]
102961418  CERS1; ceramide synthase 1 [KO:K04710] [EC:2.3.1.299]
102961437  PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
102961449  SPHK2; sphingosine kinase 2 [KO:K04718] [EC:2.7.1.91]
102961543  PPP2R1B; protein phosphatase 2 scaffold subunit Abeta [KO:K03456]
102961799  CERS5; ceramide synthase 5 [KO:K23727]
102961847  ACER2; alkaline ceramidase 2 [KO:K01441] [EC:3.5.1.23]
102961871  FCER1A; Fc fragment of IgE receptor Ia [KO:K08089]
102961922  RAC2; ras-related C3 botulinum toxin substrate 2 (rho family, small GTP binding protein Rac2) [KO:K07860]
102962016  PLD1; phospholipase D1 [KO:K01115] [EC:3.1.4.4]
102962512  SMPD2; sphingomyelin phosphodiesterase 2 [KO:K12351] [EC:3.1.4.12]
102962571  TP53; tumor protein p53 [KO:K04451]
102962946  GNAI2; G protein subunit alpha i2 [KO:K04630]
102963096  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
102963520  ROCK1; Rho associated coiled-coil containing protein kinase 1 [KO:K04514] [EC:2.7.11.39]
102963876  [KO:K08090]
102963902  ADORA3; adenosine A3 receptor [KO:K04268]
102964232  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102964338  SMPD1; sphingomyelin phosphodiesterase 1 [KO:K12350] [EC:3.1.4.12]
102964350  ORMDL3; ORMDL sphingolipid biosynthesis regulator 3 [KO:K28680]
102964498  GNA13; G protein subunit alpha 13 [KO:K04639]
102964542  PPP2R3A; protein phosphatase 2 regulatory subunit B''alpha [KO:K11583]
102964841  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102965070  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
102965334  [KO:K08090]
102966015  FCER1G; Fc fragment of IgE receptor Ig [KO:K07983]
102966104  MS4A2; membrane spanning 4-domains A2 [KO:K08090]
102966272  SPTSSB; serine palmitoyltransferase small subunit B [KO:K26384]
102966392  SPHK1; sphingosine kinase 1 [KO:K04718] [EC:2.7.1.91]
102966802  TRAF2; TNF receptor associated factor 2 [KO:K03173] [EC:2.3.2.27]
102967184  SGPP1; sphingosine-1-phosphate phosphatase 1 [KO:K04716] [EC:3.1.3.-]
102967483  GAB2; GRB2 associated binding protein 2 [KO:K08091]
102967516  NOS3; nitric oxide synthase 3 [KO:K13242] [EC:1.14.13.39]
102967709  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102968191  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102968482  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102968533  CERS3; ceramide synthase 3 [KO:K24622]
102968561  RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
102968590  PRKCA; protein kinase C alpha [KO:K02677] [EC:2.7.11.13]
102968597  TRADD; TNFRSF1A associated via death domain [KO:K03171]
102968778  ABCC1; ATP binding cassette subfamily C member 1 [KO:K05665] [EC:7.6.2.3]
102969154  ASAH1; N-acylsphingosine amidohydrolase 1 [KO:K12348] [EC:3.5.1.23]
102969757  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102970289  PPP2R2C; protein phosphatase 2 regulatory subunit Bgamma [KO:K04354]
102970444  CERS2; ceramide synthase 2 [KO:K24621]
102970893  SGMS2; sphingomyelin synthase 2 [KO:K04714] [EC:2.7.8.27 2.7.8.48 3.1.4.62]
102971823  PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
102972446  PTEN; phosphatase and tensin homolog [KO:K01110] [EC:3.1.3.16 3.1.3.48 3.1.3.67]
102972487  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102972723  DEGS1; delta 4-desaturase, sphingolipid 1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
102972870  CERS4; ceramide synthase 4 [KO:K24621]
102972900  ORMDL1; ORMDL sphingolipid biosynthesis regulator 1 [KO:K28680]
107180011  SGPP2; sphingosine-1-phosphate phosphatase 2 [KO:K04717] [EC:3.1.3.-]
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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
Reference
  Authors
Xie T, Liu P, Wu X, Dong F, Zhang Z, Yue J, Mahawar U, Farooq F, Vohra H, Fang Q, Liu W, Wattenberg BW, Gong X
  Title
Ceramide sensing by human SPT-ORMDL complex for establishing sphingolipid homeostasis.
  Journal
Nat Commun 14:3475 (2023)
DOI:10.1038/s41467-023-39274-y
Related
pathway
ptg00600  Sphingolipid metabolism
ptg04010  MAPK signaling pathway
ptg04142  Lysosome biogenesis
ptg04151  PI3K-Akt signaling pathway
KO pathway
ko04071   

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