KEGG   PATHWAY: lruf04071
Entry
lruf04071                   Pathway                                
Name
Sphingolipid signaling pathway - Lynx rufus (bobcat)
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
lruf04071  Sphingolipid signaling pathway
lruf04071

Organism
Lynx rufus (bobcat) [GN:lruf]
Gene
124512604  serine palmitoyltransferase 2 [KO:K00654] [EC:2.3.1.50]
124527885  serine palmitoyltransferase 1 [KO:K00654] [EC:2.3.1.50]
124502917  serine palmitoyltransferase 3 [KO:K00654] [EC:2.3.1.50]
124508896  serine palmitoyltransferase small subunit A [KO:K26384]
124526316  serine palmitoyltransferase small subunit B [KO:K26384]
124523045  ceramide synthase 1 isoform X1 [KO:K04710] [EC:2.3.1.299]
124514449  ceramide synthase 2 [KO:K24621] [EC:2.3.1.297]
124523586  ceramide synthase 4-like isoform X1 [KO:K24621] [EC:2.3.1.297]
124517427  ceramide synthase 3 [KO:K24622] [EC:2.3.1.297 2.3.1.298]
124501461  ceramide synthase 5 isoform X1 [KO:K23727] [EC:2.3.1.291]
124515850  ceramide synthase 6 [KO:K23727] [EC:2.3.1.291]
124510317  sphingolipid delta(4)-desaturase DES1 isoform X1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
124512525  sphingolipid delta(4)-desaturase/C4-monooxygenase DES2 isoform X1 [KO:K04712] [EC:1.14.19.17 1.14.18.5]
124505649  sphingomyelin phosphodiesterase [KO:K12350] [EC:3.1.4.12]
124518706  phosphatidylcholine:ceramide cholinephosphotransferase 1 [KO:K04714] [EC:2.7.8.27]
124520963  phosphatidylcholine:ceramide cholinephosphotransferase 2 [KO:K04714] [EC:2.7.8.27]
124528979  tumor necrosis factor [KO:K03156]
124501088  LOW QUALITY PROTEIN: tumor necrosis factor receptor superfamily member 1A-like [KO:K03158]
124507668  protein FAN isoform X1 [KO:K18953]
124528604  sphingomyelin phosphodiesterase 2 isoform X1 [KO:K12351] [EC:3.1.4.12]
124520027  acid ceramidase [KO:K12348] [EC:3.5.1.23]
124518712  neutral ceramidase isoform X1 [KO:K12349] [EC:3.5.1.23]
124524527  alkaline ceramidase 1 [KO:K01441] [EC:3.5.1.23]
124500997  alkaline ceramidase 2 isoform X1 [KO:K01441] [EC:3.5.1.23]
124511385  tumor necrosis factor receptor type 1-associated DEATH domain protein-like [KO:K03171]
124522349  TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
124527879  cathepsin D [KO:K01379] [EC:3.4.23.5]
124501306  BH3-interacting domain death agonist-like [KO:K04726]
124510927  apoptosis regulator BAX isoform X1 [KO:K02159]
124528854  mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
124520648  mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
124506951  mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
124514653  mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
124528014  mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
124528088  mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
124501588  mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
124502315  mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
124516243  protein kinase C zeta type [KO:K18952] [EC:2.7.11.13]
124510270  RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
124511119  RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124512474  RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
124517105  apoptosis regulator Bcl-2 [KO:K02161]
124520278  serine/threonine-protein phosphatase 2A catalytic subunit beta isoform [KO:K04382] [EC:3.1.3.16]
124515685  serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform isoform X1 [KO:K04382] [EC:3.1.3.16]
124510821  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform [KO:K03456]
124504617  serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform isoform X1 [KO:K03456]
124520573  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B gamma isoform [KO:K04354]
124521328  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform isoform X1 [KO:K04354]
124507238  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B delta isoform [KO:K04354]
124509561  serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform [KO:K04354]
124526952  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit alpha isoform X1 [KO:K11583]
124508907  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit gamma isoform X1 [KO:K11583]
124502874  serine/threonine-protein phosphatase 2A regulatory subunit B'' subunit beta-like [KO:K11583]
124510105  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit alpha isoform [KO:K11584]
124512134  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit epsilon isoform isoform X1 [KO:K11584]
124512512  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit gamma isoform isoform X1 [KO:K11584]
124505607  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit beta isoform isoform X1 [KO:K11584]
124528074  serine/threonine-protein phosphatase 2A 56 kDa regulatory subunit delta isoform [KO:K11584]
124519563  cellular tumor antigen p53 isoform X1 [KO:K04451]
124521846  high affinity immunoglobulin epsilon receptor subunit alpha-like [KO:K08089]
124505002  membrane-spanning 4-domains subfamily A member 3-like isoform X1 [KO:K08090]
124505547  high affinity immunoglobulin epsilon receptor subunit beta-like isoform X1 [KO:K08090]
124505741  high affinity immunoglobulin epsilon receptor subunit beta-like [KO:K08090]
124521734  high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
124528746  tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
124505335  GRB2-associated-binding protein 2 [KO:K08091]
124525968  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
124527077  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
124514827  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
124517840  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
124514527  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
124523730  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
124525987  phospholipase D1 isoform X1 [KO:K01115] [EC:3.1.4.4]
124519573  phospholipase D2 isoform X1 [KO:K01115] [EC:3.1.4.4]
124510943  sphingosine kinase 2 isoform X1 [KO:K04718] [EC:2.7.1.91]
124512822  sphingosine kinase 1-like [KO:K04718] [EC:2.7.1.91]
124526765  kininogen-2-like isoform X1 [KO:K03898]
124510399  adenosine receptor A1 [KO:K04265]
124516037  adenosine receptor A3 [KO:K04268]
124512289  B2 bradykinin receptor-like [KO:K03916]
124516085  delta-type opioid receptor [KO:K04213]
124514443  guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
124523010  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
124524167  guanine nucleotide-binding protein G(i) subunit alpha-1 isoform X1 [KO:K04630]
124503791  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4-like [KO:K05858] [EC:3.1.4.11]
124503878  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 [KO:K05858] [EC:3.1.4.11]
124505119  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
124508712  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X1 [KO:K05858] [EC:3.1.4.11]
124502915  protein kinase C epsilon type [KO:K18050] [EC:2.7.11.13]
124517731  mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
124519861  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
124512132  sphingosine-1-phosphate phosphatase 1 [KO:K04716] [EC:3.1.3.-]
124514772  sphingosine-1-phosphate phosphatase 2 [KO:K04717] [EC:3.1.3.-]
124517880  multidrug resistance-associated protein 1 isoform X1 [KO:K05665] [EC:7.6.2.3]
124506873  sphingosine-1-phosphate lyase 1 [KO:K01634] [EC:4.1.2.27]
124515207  sphingosine 1-phosphate receptor 1 [KO:K04288]
124523906  sphingosine 1-phosphate receptor 2 [KO:K04292]
124527565  GTPase HRas isoform X1 [KO:K02833]
124502703  GTPase KRas isoform X1 [KO:K07827]
124516245  GTPase NRas [KO:K07828]
124523760  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
124508471  dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
124524782  dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
124517688  3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
124524465  nitric oxide synthase, endothelial isoform X1 [KO:K13242] [EC:1.14.13.39]
124519305  ras-related C3 botulinum toxin substrate 1 [KO:K04392]
124501030  ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
124522479  ras-related C3 botulinum toxin substrate 3-like [KO:K07861]
124524848  sphingosine 1-phosphate receptor 3 [KO:K04290]
124528694  guanine nucleotide-binding protein G(q) subunit alpha isoform X1 [KO:K04634]
124513500  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
124517730  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
124527789  protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
124523511  sphingosine 1-phosphate receptor 4 isoform X1 [KO:K04293]
124524891  sphingosine 1-phosphate receptor 5-like [KO:K04295]
124519214  guanine nucleotide-binding protein subunit alpha-12 [KO:K04346]
124513497  guanine nucleotide-binding protein subunit alpha-13 [KO:K04639]
124523904  transforming protein RhoA [KO:K04513]
124517572  rho-associated protein kinase 1 isoform X1 [KO:K04514] [EC:2.7.11.1]
124504219  rho-associated protein kinase 2 [KO:K17388] [EC:2.7.11.1]
124518602  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]
124520800  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
124504954  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
lruf00600  Sphingolipid metabolism
lruf04010  MAPK signaling pathway
lruf04142  Lysosome
lruf04151  PI3K-Akt signaling pathway
KO pathway
ko04071   
LinkDB

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