KEGG   PATHWAY: cfa04722
Entry
cfa04722                    Pathway                                
Name
Neurotrophin signaling pathway - Canis lupus familiaris (dog)
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
cfa04722  Neurotrophin signaling pathway
cfa04722

Organism
Canis lupus familiaris (dog) [GN:cfa]
Gene
100682628  BEX3; protein BEX3 [KO:K12465]
100683018  SH2B3; SH2B adapter protein 3 isoform X2 [KO:K12459]
100683481  [KO:K07293] [EC:3.1.3.48]
100684140  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
100684309  CRK; adapter molecule crk isoform X8 [KO:K04438]
100688110  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
100855877  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100856261  NTRK3; NT-3 growth factor receptor isoform X1 [KO:K05101] [EC:2.7.10.1]
100856339  [KO:K02649]
102153034  [KO:K02183]
102154776  ZNF274; neurotrophin receptor-interacting factor homolog isoform X1 [KO:K12458]
102155642  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
119863888  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
119866928  [KO:K04393]
403402  NGF; beta-nerve growth factor precursor [KO:K02582]
403408  PSEN1; presenilin-1 isoform 1 [KO:K04505] [EC:3.4.23.-]
403416  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
403461  BDNF; brain-derived neurotrophic factor precursor [KO:K04355]
403523  BAX; apoptosis regulator BAX [KO:K02159]
403735  HRAS; GTPase HRas isoform 1 [KO:K02833]
403856  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
403869  TP53; cellular tumor antigen p53 [KO:K04451]
403871  KRAS; GTPase KRas isoform X1 [KO:K07827]
403872  NRAS; GTPase NRas [KO:K07828]
403954  RHOA; transforming protein RhoA [KO:K04513]
403955  RAC1; ras-related C3 botulinum toxin substrate 1 precursor [KO:K04392]
442859  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
442964  AKT3; RAC-gamma serine/threonine-protein kinase isoform X8 [KO:K04456] [EC:2.7.11.1]
442968  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
449021  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
474444  FRS2; fibroblast growth factor receptor substrate 2 isoform X1 [KO:K12461]
474503  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
474584  CALM2; calmodulin-2 [KO:K02183]
474652  MAPK9; mitogen-activated protein kinase 9 isoform X4 [KO:K04440] [EC:2.7.11.24]
475526  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
475657  KIDINS220; kinase D-interacting substrate of 220 kDa isoform X56 [KO:K12460]
475924  ARHGDIA; rho GDP-dissociation inhibitor 1 [KO:K12462]
476215  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
476352  SHC3; SHC-transforming protein 3 [KO:K17448]
476428  CALM3; calmodulin-3 isoform X2 [KO:K02183]
477085  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
477488  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
477575  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
477746  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
477936  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
478061  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
478347  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
478351  CALML4; calmodulin-like protein 4 isoform X2 [KO:K02183]
478464  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
478575  GSK3B; glycogen synthase kinase-3 beta isoform X13 [KO:K03083] [EC:2.7.11.26]
479875  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X3 [KO:K06276] [EC:2.7.11.1]
479915  SORT1; sortilin isoform X1 [KO:K12388]
480291  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
480416  CALM1; calmodulin-1 [KO:K02183]
480481  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X8 [KO:K04421] [EC:2.7.11.25]
480645  YWHAE; 14-3-3 protein epsilon isoform X2 [KO:K06630]
480923  MAGED1; melanoma-associated antigen D1 isoform X2 [KO:K12464]
481150  IRAK3; interleukin-1 receptor-associated kinase 3 [KO:K04732] [EC:2.7.11.1]
481291  PRDM4; PR domain zinc finger protein 4 isoform X1 [KO:K12463] [EC:2.1.1.-]
481954  FOXO3; forkhead box protein O3 [KO:K09408]
482687  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
482839  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
483225  RAP1A; ras-related protein Rap-1A isoform X1 [KO:K04353]
483312  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
483729  RELA; transcription factor p65 isoform X2 [KO:K04735]
483763  BAD; bcl2-associated agonist of cell death [KO:K02158]
483808  GAB1; GRB2-associated-binding protein 1 isoform X5 [KO:K09593]
484147  NTRK2; BDNF/NT-3 growth factors receptor isoform X2 [KO:K04360] [EC:2.7.10.1]
484519  NFKBIB; NF-kappa-B inhibitor beta isoform X2 [KO:K02581]
484648  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
484657  IRAK2; interleukin-1 receptor-associated kinase-like 2 isoform X2 [KO:K04731] [EC:2.7.11.1]
485004  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
485874  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
486148  IRS1; insulin receptor substrate 1 [KO:K16172]
486601  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X2 [KO:K04733] [EC:2.7.11.1]
486666  ARHGDIB; rho GDP-dissociation inhibitor 2 [KO:K12462]
486731  NTF3; neurotrophin-3 isoform X2 [KO:K04356]
487146  CALML5; calmodulin-like protein 5 [KO:K02183]
487235  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
487353  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X2 [KO:K04373] [EC:2.7.11.1]
487546  SHC4; SHC-transforming protein 4 isoform X2 [KO:K17449]
488084  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
489050  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
489532  MAPK7; mitogen-activated protein kinase 7 isoform X2 [KO:K04464] [EC:2.7.11.24]
489620  TP73; tumor protein p73 isoform X28 [KO:K10148]
489644  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X3 [KO:K00922] [EC:2.7.1.153]
489692  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
489820  SH2B2; SH2B adapter protein 2 isoform X1 [KO:K07193]
490263  MAPKAPK2; MAP kinase-activated protein kinase 2 isoform X2 [KO:K04443] [EC:2.7.11.1]
490382  PSEN2; presenilin-2 [KO:K04522] [EC:3.4.23.-]
490404  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
490439  SHC1; SHC-transforming protein 1 [KO:K06279]
490682  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
490831  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X3 [KO:K04445] [EC:2.7.11.1]
490878  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
491071  NGFR; tumor necrosis factor receptor superfamily member 16 isoform X3 [KO:K02583]
491286  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
491292  ABL1; tyrosine-protein kinase ABL1 isoform X2 [KO:K06619] [EC:2.7.10.2]
491989  RPS6KA6; ribosomal protein S6 kinase alpha-6 isoform X1 [KO:K04373] [EC:2.7.11.1]
492247  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
494005  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
607019  MAPK11; mitogen-activated protein kinase 11 isoform X2 [KO:K04441] [EC:2.7.11.24]
607023  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
607269  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
608125  CRKL; crk-like protein isoform X2 [KO:K04438]
608573  [KO:K06630]
608981  RAP1B; ras-related protein Rap-1b [KO:K07836]
609429  JUN; transcription factor AP-1 [KO:K04448]
609559  MAP2K5; dual specificity mitogen-activated protein kinase kinase 5 isoform X3 [KO:K04463] [EC:2.7.12.2]
609956  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
610764  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515] [EC:2.7.11.17]
611541  ARHGDIG; rho GDP-dissociation inhibitor 3 isoform X1 [KO:K12462]
611939  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
611955  SHC2; SHC-transforming protein 2 isoform X2 [KO:K17447]
611999  MATK; megakaryocyte-associated tyrosine-protein kinase isoform X1 [KO:K08888] [EC:2.7.10.2]
612448  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X1 [KO:K04373] [EC:2.7.11.1]
612792  SH2B1; SH2B adapter protein 1 isoform X5 [KO:K12459]
612821  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
612941  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
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
cfa04010  MAPK signaling pathway
cfa04120  Ubiquitin mediated proteolysis
cfa04210  Apoptosis
cfa04720  Long-term potentiation
cfa04810  Regulation of actin cytoskeleton
KO pathway
ko04722   

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