KEGG   PATHWAY: pon04722
Entry
pon04722                    Pathway                                
Name
Neurotrophin signaling pathway - Pongo abelii (Sumatran orangutan)
Description
Neurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4). Neurotrophins exert their functions through engagement of Trk tyrosine kinase receptors or p75 neurotrophin receptor (p75NTR). Neurotrophin/Trk signaling is regulated by connecting a variety of intracellular signaling cascades, which include MAPK pathway, PI-3 kinase pathway, and PLC pathway, transmitting positive signals like enhanced survival and growth. On the other hand, p75NTR transmits both positive and nagative signals. These signals play an important role for neural development and additional higher-order activities such as learning and memory.
Class
Organismal Systems; Nervous system
Pathway map
pon04722  Neurotrophin signaling pathway
pon04722

Organism
Pongo abelii (Sumatran orangutan) [GN:pon]
Gene
100441497  NGF; beta-nerve growth factor isoform X2 [KO:K02582]
100447350  BDNF; brain-derived neurotrophic factor isoform X1 [KO:K04355]
100457557  LOW QUALITY PROTEIN: neurotrophin-4 [KO:K12457]
103888645  NTF4; neurotrophin-4 [KO:K12457]
100432172  NTF3; neurotrophin-3 [KO:K04356]
100452269  NTRK1; high affinity nerve growth factor receptor isoform X2 [KO:K03176] [EC:2.7.10.1]
100441207  NTRK2; BDNF/NT-3 growth factors receptor isoform X2 [KO:K04360] [EC:2.7.10.1]
100458353  NTRK3; NT-3 growth factor receptor isoform X3 [KO:K05101] [EC:2.7.10.1]
100443516  SH2B2; SH2B adapter protein 2 isoform X1 [KO:K07193]
100433195  SH2B3; SH2B adapter protein 3 isoform X2 [KO:K12459]
100456313  SH2B1; SH2B adapter protein 1 isoform X1 [KO:K12459]
100173972  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100434331  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
100458733  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
100459427  HRAS; GTPase HRas [KO:K02833]
100462513  KRAS; GTPase KRas isoform X1 [KO:K07827]
100174317  NRAS; GTPase NRas precursor [KO:K07828]
100173732  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
100442288  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
100446021  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100450988  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100169740  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100431824  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100438726  RPS6KA6; ribosomal protein S6 kinase alpha-6 isoform X1 [KO:K04373] [EC:2.7.11.1]
100450481  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X2 [KO:K04373] [EC:2.7.11.1]
100451332  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X1 [KO:K04373] [EC:2.7.11.1]
100459459  RPS6KA1; ribosomal protein S6 kinase alpha-1 [KO:K04373] [EC:2.7.11.1]
100173967  RPS6KA5; ribosomal protein S6 kinase alpha-5 [KO:K04445] [EC:2.7.11.1]
100462459  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100431578  cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
100938429  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
100172014  KIDINS220; LOW QUALITY PROTEIN: kinase D-interacting substrate of 220 kDa [KO:K12460]
100452012  FRS2; fibroblast growth factor receptor substrate 2 [KO:K12461]
100452410  CRK; adapter molecule crk isoform X1 [KO:K04438]
100443298  CRKL; crk-like protein [KO:K04438]
100444262  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
100433839  RAP1A; ras-related protein Rap-1A [KO:K04353]
100171907  RAP1B; ras-related protein Rap-1b precursor [KO:K07836]
100444678  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X3 [KO:K04421] [EC:2.7.11.25]
100449213  MAP2K5; dual specificity mitogen-activated protein kinase kinase 5 isoform X1 [KO:K04463] [EC:2.7.12.2]
100451029  MAPK7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:2.7.11.24]
100449269  MAPK14; mitogen-activated protein kinase 14 isoform X2 [KO:K04441] [EC:2.7.11.24]
100449853  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
100437263  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
100438358  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100446757  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
100173225  SHC1; SHC-transforming protein 1 [KO:K06279]
100445042  SHC2; SHC-transforming protein 2 [KO:K17447]
100462011  SHC3; SHC-transforming protein 3 [KO:K17448]
100431574  SHC4; SHC-transforming protein 4 [KO:K17449]
100458884  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
100174298  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
100173589  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
100437617  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100432846  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100453779  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103889133  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100454279  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100448114  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100442100  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100454648  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
100459445  NF-kappa-B inhibitor alpha [KO:K04734]
100446325  NFKBIE; LOW QUALITY PROTEIN: NF-kappa-B inhibitor epsilon [KO:K05872]
100461595  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100456049  RELA; transcription factor p65 [KO:K04735]
100451077  FOXO3; forkhead box protein O3 [KO:K09408]
100461418  FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
100454097  BAD; bcl2-associated agonist of cell death [KO:K02158]
100447772  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
100452403  LOW QUALITY PROTEIN: 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
112129400  LOW QUALITY PROTEIN: putative 3-phosphoinositide-dependent protein kinase 2 [KO:K06276] [EC:2.7.11.1]
100442255  IRS1; insulin receptor substrate 1 [KO:K16172]
100450941  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116] [EC:3.1.4.11]
100457650  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
100452668  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
100436432  CALML5; calmodulin-like protein 5 [KO:K02183]
100436811  CALML3; calmodulin-like protein 3 [KO:K02183]
100444426  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
100172680  CALM1; calmodulin [KO:K02183]
100173214  CALM2; calmodulin [KO:K02183]
100172890  CALM3; calmodulin [KO:K02183]
100451658  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
100455662  calmodulin-alpha-like [KO:K02183]
103892390  calmodulin-like [KO:K02183]
100433531  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
100172212  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
100462386  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
100436747  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
100461605  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
100453216  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
100440983  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
100437723  MATK; megakaryocyte-associated tyrosine-protein kinase isoform X1 [KO:K08888] [EC:2.7.10.2]
100456038  NGFR; tumor necrosis factor receptor superfamily member 16 [KO:K02583]
100434317  ARHGDIB; rho GDP-dissociation inhibitor 2 [KO:K12462]
100449358  ARHGDIA; rho GDP-dissociation inhibitor 1 isoform X2 [KO:K12462]
100433846  ARHGDIG; rho GDP-dissociation inhibitor 3 [KO:K12462]
100171605  RHOA; transforming protein RhoA precursor [KO:K04513]
100438199  CDC42; cell division control protein 42 homolog [KO:K04393]
100443271  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
100453309  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
100458776  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
100431600  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X2 [KO:K04431] [EC:2.7.12.2]
100174482  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
100459133  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
100437424  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100450292  JUN; transcription factor AP-1 [KO:K04448]
100435218  TP53; cellular tumor antigen p53 [KO:K04451]
100450682  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
100433100  TP73; tumor protein p73 isoform X1 [KO:K10148]
100449432  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
100435244  ZNF274; neurotrophin receptor-interacting factor homolog isoform X1 [KO:K12458]
100173737  PRDM4; PR domain zinc finger protein 4 [KO:K12463] [EC:2.1.1.-]
100446209  MAGED1; melanoma-associated antigen D1 [KO:K12464]
100446446  LOW QUALITY PROTEIN: protein BEX3 [KO:K12465]
112130790  BEX3; protein BEX3 isoform X1 [KO:K12465]
100455220  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
112131710  14-3-3 protein epsilon-like isoform X1 [KO:K06630]
100448203  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
100437883  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X2 [KO:K04730] [EC:2.7.11.1]
100454140  IRAK2; interleukin-1 receptor-associated kinase-like 2 isoform X1 [KO:K04731] [EC:2.7.11.1]
100441850  IRAK3; interleukin-1 receptor-associated kinase 3 [KO:K04732] [EC:2.7.11.1]
100447243  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
100440586  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X3 [KO:K07209] [EC:2.7.11.10]
100457993  SORT1; sortilin isoform X1 [KO:K12388]
100173083  PSEN1; presenilin-1 [KO:K04505] [EC:3.4.23.-]
100172138  PSEN2; presenilin-2 [KO:K04522] [EC:3.4.23.-]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00195  N-Acylsphingosine
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:12676795
  Authors
Huang EJ, Reichardt LF.
  Title
Trk receptors: roles in neuronal signal transduction.
  Journal
Annu Rev Biochem 72:609-42 (2003)
DOI:10.1146/annurev.biochem.72.121801.161629
Reference
PMID:11399424
  Authors
Patapoutian A, Reichardt LF
  Title
Trk receptors: mediators of neurotrophin action.
  Journal
Curr Opin Neurobiol 11:272-80 (2001)
DOI:10.1016/S0959-4388(00)00208-7
Reference
PMID:16699811
  Authors
Arevalo JC, Wu SH
  Title
Neurotrophin signaling: many exciting surprises!
  Journal
Cell Mol Life Sci 63:1523-37 (2006)
DOI:10.1007/s00018-006-6010-1
Reference
PMID:14704852
  Authors
Teng KK, Hempstead BL
  Title
Neurotrophins and their receptors: signaling trios in complex biological systems.
  Journal
Cell Mol Life Sci 61:35-48 (2004)
DOI:10.1007/s00018-003-3099-3
Reference
PMID:11529497
  Authors
Miller FD, Kaplan DR
  Title
Neurotrophin signalling pathways regulating neuronal apoptosis.
  Journal
Cell Mol Life Sci 58:1045-53 (2001)
DOI:10.1007/PL00000919
Reference
PMID:10851172
  Authors
Kaplan DR, Miller FD
  Title
Neurotrophin signal transduction in the nervous system.
  Journal
Curr Opin Neurobiol 10:381-91 (2000)
DOI:10.1016/S0959-4388(00)00092-1
Reference
PMID:16939974
  Authors
Reichardt LF
  Title
Neurotrophin-regulated signalling pathways.
  Journal
Philos Trans R Soc Lond B Biol Sci 361:1545-64 (2006)
DOI:10.1098/rstb.2006.1894
Reference
PMID:16856873
  Authors
Zampieri N, Chao MV
  Title
Mechanisms of neurotrophin receptor signalling.
  Journal
Biochem Soc Trans 34:607-11 (2006)
DOI:10.1042/BST0340607
Reference
PMID:15499580
  Authors
Rose CR, Blum R, Kafitz KW, Kovalchuk Y, Konnerth A
  Title
From modulator to mediator: rapid effects of BDNF on ion channels.
  Journal
Bioessays 26:1185-94 (2004)
DOI:10.1002/bies.20118
Reference
PMID:10812966
  Authors
Yano H, Chao MV
  Title
Neurotrophin receptor structure and interactions.
  Journal
Pharm Acta Helv 74:253-60 (2000)
DOI:10.1016/s0031-6865(99)00036-9
Reference
PMID:10764727
  Authors
Mukai J, Hachiya T, Shoji-Hoshino S, Kimura MT, Nadano D, Suvanto P, Hanaoka T, Li Y, Irie S, Greene LA, Sato TA
  Title
NADE, a p75NTR-associated cell death executor, is involved in signal transduction mediated by the common neurotrophin receptor p75NTR.
  Journal
J Biol Chem 275:17566-70 (2000)
DOI:10.1074/jbc.C000140200
Reference
PMID:10985348
  Authors
Salehi AH, Roux PP, Kubu CJ, Zeindler C, Bhakar A, Tannis LL, Verdi JM, Barker PA
  Title
NRAGE, a novel MAGE protein, interacts with the p75 neurotrophin receptor and facilitates nerve growth factor-dependent apoptosis.
  Journal
Neuron 27:279-88 (2000)
DOI:10.1016/S0896-6273(00)00036-2
Related
pathway
pon04010  MAPK signaling pathway
pon04120  Ubiquitin mediated proteolysis
pon04210  Apoptosis
pon04720  Long-term potentiation
pon04810  Regulation of actin cytoskeleton
KO pathway
ko04722   
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