KEGG   PATHWAY: ecb04722
Entry
ecb04722                    Pathway                                
Name
Neurotrophin signaling pathway - Equus caballus (horse)
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
ecb04722  Neurotrophin signaling pathway
ecb04722

Organism
Equus caballus (horse) [GN:ecb]
Gene
100065669  NGF; beta-nerve growth factor [KO:K02582]
100009689  BDNF; brain-derived neurotrophic factor precursor [KO:K04355]
100054859  NTF4; neurotrophin-4 [KO:K12457]
100051839  NTF3; neurotrophin-3 isoform X2 [KO:K04356]
100064594  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
100061700  NTRK2; BDNF/NT-3 growth factors receptor isoform X3 [KO:K04360] [EC:2.7.10.1]
100069852  NTRK3; NT-3 growth factor receptor isoform X2 [KO:K05101] [EC:2.7.10.1]
100059630  SH2B adapter protein 2 isoform X1 [KO:K07193]
100064371  SH2B1; SH2B adapter protein 1 isoform X5 [KO:K12459]
100057885  SH2B3; SH2B adapter protein 3 isoform X1 [KO:K12459]
100051866  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100053889  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
100066282  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
100055481  HRAS; GTPase HRas isoform X1 [KO:K02833]
100064473  KRAS; GTPase KRas isoform X1 [KO:K07827]
100051785  LOW QUALITY PROTEIN: GTPase KRas-like [KO:K07827]
100059469  NRAS; GTPase NRas [KO:K07828]
100051110  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100065760  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
100065996  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
100063190  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100057701  MAPK1; mitogen-activated protein kinase 1 isoform X2 [KO:K04371] [EC:2.7.11.24]
100066173  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100058911  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X1 [KO:K04373] [EC:2.7.11.1]
100057166  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X1 [KO:K04373] [EC:2.7.11.1]
100050176  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X1 [KO:K04373] [EC:2.7.11.1]
100072397  RPS6KA6; ribosomal protein S6 kinase alpha-6 isoform X1 [KO:K04373] [EC:2.7.11.1]
100062953  RPS6KA5; ribosomal protein S6 kinase alpha-5 [KO:K04445] [EC:2.7.11.1]
100070334  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100050934  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
100057204  KIDINS220; kinase D-interacting substrate of 220 kDa isoform X1 [KO:K12460]
100052205  FRS2; fibroblast growth factor receptor substrate 2 [KO:K12461]
100072356  CRK; adapter molecule crk isoform X1 [KO:K04438]
100050855  CRKL; crk-like protein [KO:K04438]
100069527  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X8 [KO:K06277]
100049912  ras-related protein Rap-1A [KO:K04353]
100058930  RAP1A; ras-related protein Rap-1A [KO:K04353]
100052025  RAP1B; ras-related protein Rap-1b [KO:K07836]
100064751  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
100052849  MAP2K5; dual specificity mitogen-activated protein kinase kinase 5 isoform X8 [KO:K04463] [EC:2.7.12.2]
100073174  MAPK7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:2.7.11.24]
100056278  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
100056239  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100063532  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
106782258  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100055510  MAPKAPK2; LOW QUALITY PROTEIN: MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
102147500  MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
100063053  SHC1; SHC-transforming protein 1 isoform X2 [KO:K06279]
100146209  SHC2; SHC-transforming protein 2 [KO:K17447]
100061926  SHC3; SHC-transforming protein 3 [KO:K17448]
100055699  SHC4; SHC-transforming protein 4 [KO:K17449]
100062924  GAB1; GRB2-associated-binding protein 1 isoform X2 [KO:K09593]
100052122  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100050227  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
100146348  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100051623  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100058141  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100051753  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100064671  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100054961  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100061130  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100064368  NFKBIB; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
100058000  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100067767  NFKBIE; LOW QUALITY PROTEIN: NF-kappa-B inhibitor epsilon [KO:K05872]
100067894  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X4 [KO:K02580]
100057483  RELA; transcription factor p65 [KO:K04735]
100066558  FOXO3; forkhead box protein O3 [KO:K09408]
100052326  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
100055447  BAD; bcl2-associated agonist of cell death [KO:K02158]
100061033  GSK3B; glycogen synthase kinase-3 beta isoform X6 [KO:K03083] [EC:2.7.11.26]
100630736  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
100061987  IRS1; insulin receptor substrate 1 [KO:K16172]
100070545  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X3 [KO:K01116] [EC:3.1.4.11]
100055670  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X2 [KO:K05859] [EC:3.1.4.11]
100051333  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
100057133  CALML5; calmodulin-like protein 5 [KO:K02183]
100062752  CALM1; calmodulin-1 [KO:K02183]
100070422  calmodulin-like protein 3 [KO:K02183]
100071150  CALM3; calmodulin-3 [KO:K02183]
100629145  CALM2; calmodulin-2 [KO:K02183]
100064482  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
100052798  CALML4; calmodulin-like protein 4 isoform X2 [KO:K02183]
100064138  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X13 [KO:K04515] [EC:2.7.11.17]
100071654  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
100072618  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X6 [KO:K04515] [EC:2.7.11.17]
100146368  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
100073192  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
100069715  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
100056857  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
100146191  tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
100146548  MATK; megakaryocyte-associated tyrosine-protein kinase isoform X1 [KO:K08888] [EC:2.7.10.2]
100069694  NGFR; tumor necrosis factor receptor superfamily member 16 [KO:K02583]
100064001  ARHGDIB; rho GDP-dissociation inhibitor 2 [KO:K12462]
100049942  ARHGDIA; rho GDP-dissociation inhibitor 1 [KO:K12462]
100146456  ARHGDIG; rho GDP-dissociation inhibitor 3 [KO:K12462]
100053343  RHOA; transforming protein RhoA [KO:K04513]
100058188  CDC42; cell division control protein 42 homolog [KO:K04393]
100061732  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
100061688  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
100073186  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
100147230  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
100052608  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
100057961  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
100051798  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100067469  JUN; transcription factor AP-1 [KO:K04448]
100062044  TP53; cellular tumor antigen p53 [KO:K04451]
100054674  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
100052597  TP73; tumor protein p73 [KO:K10148]
100052296  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
100147674  ZNF274; neurotrophin receptor-interacting factor homolog isoform X1 [KO:K12458]
100054098  PRDM4; PR domain zinc finger protein 4 isoform X1 [KO:K12463] [EC:2.1.1.-]
100147318  MAGED1; melanoma-associated antigen D1 [KO:K12464]
100059187  BEX3; protein BEX3 isoform X3 [KO:K12465]
100059962  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
100051086  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X2 [KO:K08846] [EC:2.7.11.1]
100059262  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
100058093  IRAK2; interleukin-1 receptor-associated kinase-like 2 isoform X1 [KO:K04731] [EC:2.7.11.1]
100058026  IRAK3; interleukin-1 receptor-associated kinase 3 isoform X1 [KO:K04732] [EC:2.7.11.1]
100054848  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
100050167  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
100061385  SORT1; sortilin isoform X3 [KO:K12388]
100050164  PSEN1; presenilin-1 isoform X1 [KO:K04505] [EC:3.4.23.-]
100054506  PSEN2; presenilin-2 isoform X3 [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
ecb04010  MAPK signaling pathway
ecb04120  Ubiquitin mediated proteolysis
ecb04210  Apoptosis
ecb04720  Long-term potentiation
ecb04810  Regulation of actin cytoskeleton
KO pathway
ko04722   
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