KEGG   PATHWAY: mcf04722
Entry
mcf04722                    Pathway                                
Name
Neurotrophin signaling pathway - Macaca fascicularis (crab-eating macaque)
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
mcf04722  Neurotrophin signaling pathway
mcf04722

Organism
Macaca fascicularis (crab-eating macaque) [GN:mcf]
Gene
102132327  NGF; beta-nerve growth factor [KO:K02582]
102126294  BDNF; brain-derived neurotrophic factor isoform X1 [KO:K04355]
102139472  neurotrophin-4 [KO:K12457]
102128547  NTF3; neurotrophin-3 isoform X2 [KO:K04356]
102129364  NTRK1; high affinity nerve growth factor receptor isoform X1 [KO:K03176] [EC:2.7.10.1]
102132446  NTRK2; BDNF/NT-3 growth factors receptor isoform X1 [KO:K04360] [EC:2.7.10.1]
102122449  NTRK3; NT-3 growth factor receptor isoform X1 [KO:K05101] [EC:2.7.10.1]
102121730  SH2B2; SH2B adapter protein 2 isoform X1 [KO:K07193]
102118836  SH2B3; SH2B adapter protein 3 isoform X1 [KO:K12459]
102147269  SH2B1; SH2B adapter protein 1 isoform X1 [KO:K12459]
102118276  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
102135079  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
102138313  SOS2; son of sevenless homolog 2 [KO:K03099]
102118744  HRAS; GTPase HRas isoform X1 [KO:K02833]
102131483  KRAS; GTPase KRas isoform X1 [KO:K07827]
102137913  NRAS; GTPase NRas [KO:K07828]
102125312  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101866436  BRAF; serine/threonine-protein kinase B-raf isoform X4 [KO:K04365] [EC:2.7.11.1]
102141214  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102140855  dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
102145011  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102116996  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
102138330  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X1 [KO:K04373] [EC:2.7.11.1]
102118317  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X1 [KO:K04373] [EC:2.7.11.1]
102134699  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X3 [KO:K04373] [EC:2.7.11.1]
102142347  RPS6KA6; ribosomal protein S6 kinase alpha-6 isoform X1 [KO:K04373] [EC:2.7.11.1]
102137672  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
102117938  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102138212  BCL2; apoptosis regulator Bcl-2 isoform X2 [KO:K02161]
101925345  KIDINS220; kinase D-interacting substrate of 220 kDa isoform X1 [KO:K12460]
102142977  FRS2; fibroblast growth factor receptor substrate 2 [KO:K12461]
102122623  CRKL; crk-like protein [KO:K04438]
101865065  CRK; adapter molecule crk isoform X1 [KO:K04438]
102137533  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
102144586  RAP1A; ras-related protein Rap-1A isoform X3 [KO:K04353]
102133022  RAP1B; ras-related protein Rap-1b isoform X1 [KO:K07836]
102132095  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
102118759  MAP2K5; dual specificity mitogen-activated protein kinase kinase 5 isoform X4 [KO:K04463] [EC:2.7.12.2]
102133212  MAPK7; mitogen-activated protein kinase 7 isoform X3 [KO:K04464] [EC:2.7.11.24]
101867352  MAPK13; mitogen-activated protein kinase 13 isoform X2 [KO:K04441] [EC:2.7.11.24]
101926770  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
102134421  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
101867305  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
102131033  MAPKAPK2; MAP kinase-activated protein kinase 2 isoform X2 [KO:K04443] [EC:2.7.11.1]
102142777  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
102125325  SHC2; SHC-transforming protein 2 [KO:K17447]
102130150  SHC3; SHC-transforming protein 3 [KO:K17448]
102130383  SHC4; SHC-transforming protein 4 [KO:K17449]
101865745  GAB1; GRB2-associated-binding protein 1 isoform X2 [KO:K09593]
102137291  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
101866246  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
102124804  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
102143464  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
102142026  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
102122725  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
102144461  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
102142406  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102132744  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
102130059  NFKBIB; NF-kappa-B inhibitor beta isoform X2 [KO:K02581]
101867458  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
102130086  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
102138273  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
101867324  RELA; transcription factor p65 isoform X1 [KO:K04735]
101925779  FOXO3; forkhead box protein O3 [KO:K09408]
102139406  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
102121921  BAD; bcl2-associated agonist of cell death [KO:K02158]
102133756  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
101866379  3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
102117978  IRS1; insulin receptor substrate 1 [KO:K16172]
102138726  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
102117471  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
102136158  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
102119159  CALML6; calmodulin-like protein 6 [KO:K02183]
102114795  CALML3; calmodulin-like protein 3 [KO:K02183]
102146976  CALML5; calmodulin-like protein 5 [KO:K02183]
102131162  CALM1; calmodulin-1 [KO:K02183]
101866377  CALM3; calmodulin-3 [KO:K02183]
101865168  CALM2; calmodulin-2 [KO:K02183]
102122343  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
102144138  calmodulin-1 [KO:K02183]
101926613  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
102126681  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
101865637  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
101866326  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
101864901  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
102115803  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
102129572  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X2 [KO:K07293] [EC:3.1.3.48]
102136833  MATK; megakaryocyte-associated tyrosine-protein kinase isoform X2 [KO:K08888] [EC:2.7.10.2]
102115306  NGFR; tumor necrosis factor receptor superfamily member 16 [KO:K02583]
102140490  ARHGDIB; rho GDP-dissociation inhibitor 2 [KO:K12462]
102142597  ARHGDIG; rho GDP-dissociation inhibitor 3 isoform X1 [KO:K12462]
101866857  ARHGDIA; rho GDP-dissociation inhibitor 1 [KO:K12462]
101865630  RHOA; transforming protein RhoA [KO:K04513]
101925934  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
102125726  cell division control protein 42 homolog [KO:K04393]
102124817  cell division control protein 42 homolog [KO:K04393]
101866593  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
102134837  ras-related C3 botulinum toxin substrate 1-like [KO:K04392]
102123041  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X3 [KO:K04416] [EC:2.7.11.25]
101925657  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
102126975  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X2 [KO:K04431] [EC:2.7.12.2]
102118497  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
102126339  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
102121272  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
102126446  JUN; transcription factor AP-1 [KO:K04448]
102135998  TP53; cellular tumor antigen p53 isoform X2 [KO:K04451]
102132255  BAX; apoptosis regulator BAX isoform X6 [KO:K02159]
102124774  TP73; tumor protein p73 isoform X1 [KO:K10148]
102128596  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
101867030  ZNF274; neurotrophin receptor-interacting factor homolog isoform X1 [KO:K12458]
102134175  PRDM4; PR domain zinc finger protein 4 isoform X1 [KO:K12463] [EC:2.1.1.-]
102138622  MAGED1; melanoma-associated antigen D1 [KO:K12464]
102120889  BEX3; protein BEX3 isoform X1 [KO:K12465]
101865451  14-3-3 protein epsilon [KO:K06630]
102140425  YWHAE; LOW QUALITY PROTEIN: 14-3-3 protein epsilon [KO:K06630]
102141511  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
102134829  IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
102135140  IRAK2; interleukin-1 receptor-associated kinase-like 2 isoform X2 [KO:K04731] [EC:2.7.11.1]
102119968  IRAK3; interleukin-1 receptor-associated kinase 3 isoform X1 [KO:K04732] [EC:2.7.11.1]
102140231  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
102146604  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X2 [KO:K07209] [EC:2.7.11.10]
102123074  SORT1; sortilin isoform X1 [KO:K12388]
102138674  PSEN1; presenilin-1 isoform X1 [KO:K04505] [EC:3.4.23.-]
102117766  PSEN2; presenilin-2 isoform X1 [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
mcf04010  MAPK signaling pathway
mcf04120  Ubiquitin mediated proteolysis
mcf04210  Apoptosis
mcf04720  Long-term potentiation
mcf04810  Regulation of actin cytoskeleton
KO pathway
ko04722   
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