KEGG   PATHWAY: oga04722
Entry
oga04722                    Pathway                                
Name
Neurotrophin signaling pathway - Otolemur garnettii (small-eared galago)
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
oga04722  Neurotrophin signaling pathway
oga04722

Organism
Otolemur garnettii (small-eared galago) [GN:oga]
Gene
100946218  NGF; beta-nerve growth factor [KO:K02582]
100958946  BDNF; brain-derived neurotrophic factor isoform X2 [KO:K04355]
100955816  NTF4; neurotrophin-4 [KO:K12457]
100958737  NTF3; neurotrophin-3 [KO:K04356]
100940422  NTRK1; high affinity nerve growth factor receptor isoform X2 [KO:K03176] [EC:2.7.10.1]
100956865  NTRK2; BDNF/NT-3 growth factors receptor isoform X1 [KO:K04360] [EC:2.7.10.1]
100951544  NTRK3; NT-3 growth factor receptor isoform X2 [KO:K05101] [EC:2.7.10.1]
100964578  SH2B2; LOW QUALITY PROTEIN: SH2B adapter protein 2 [KO:K07193]
100952321  SH2B1; SH2B adapter protein 1 isoform X4 [KO:K12459]
100953481  SH2B3; SH2B adapter protein 3 isoform X2 [KO:K12459]
100948701  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100958517  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
100943020  SOS2; son of sevenless homolog 2 [KO:K03099]
100951644  HRAS; GTPase HRas isoform X1 [KO:K02833]
100953050  KRAS; GTPase KRas isoform X3 [KO:K07827]
100949583  NRAS; GTPase NRas isoform X1 [KO:K07828]
100941062  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100955336  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
100959926  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
100956072  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X2 [KO:K04369] [EC:2.7.12.2]
100951533  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100957343  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100950673  RPS6KA6; LOW QUALITY PROTEIN: ribosomal protein S6 kinase alpha-6 [KO:K04373] [EC:2.7.11.1]
100945202  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X3 [KO:K04373] [EC:2.7.11.1]
100963421  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X5 [KO:K04373] [EC:2.7.11.1]
100946311  RPS6KA2; ribosomal protein S6 kinase alpha-2 [KO:K04373] [EC:2.7.11.1]
100964034  RPS6KA5; ribosomal protein S6 kinase alpha-5 [KO:K04445] [EC:2.7.11.1]
100940993  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100955447  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100942593  KIDINS220; kinase D-interacting substrate of 220 kDa [KO:K12460]
100956213  FRS2; fibroblast growth factor receptor substrate 2 [KO:K12461]
100958636  CRK; adapter molecule crk isoform X1 [KO:K04438]
100951208  CRKL; crk-like protein [KO:K04438]
100965849  RAPGEF1; rap guanine nucleotide exchange factor 1 [KO:K06277]
100962069  RAP1A; ras-related protein Rap-1A [KO:K04353]
100959791  RAP1B; ras-related protein Rap-1b [KO:K07836]
100941765  ras-related protein Rap-1b-like protein [KO:K07836]
100944704  MAP3K3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
100963374  MAP2K5; dual specificity mitogen-activated protein kinase kinase 5 isoform X2 [KO:K04463] [EC:2.7.12.2]
100962878  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
100956269  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
100957118  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100963993  MAPK11; mitogen-activated protein kinase 11 isoform X2 [KO:K04441] [EC:2.7.11.24]
100964304  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
100966784  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
100966694  SHC1; SHC-transforming protein 1 isoform X2 [KO:K06279]
100957623  SHC2; SHC-transforming protein 2 [KO:K17447]
100952749  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
100945538  SHC4; SHC-transforming protein 4 [KO:K17449]
100949240  GAB1; GRB2-associated-binding protein 1 isoform X2 [KO:K09593]
100956838  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649]
100952580  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
100949858  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
100947138  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100953367  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100954109  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100959825  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
100955276  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100945977  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100942572  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
100947991  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
100961213  NFKBIE; LOW QUALITY PROTEIN: NF-kappa-B inhibitor epsilon [KO:K05872]
100951061  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100957990  RELA; transcription factor p65 isoform X3 [KO:K04735]
100948347  FOXO3; forkhead box protein O3 [KO:K09408]
100951008  FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
100962306  BAD; bcl2-associated agonist of cell death [KO:K02158]
100952751  GSK3B; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
100950210  PDPK1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
100958778  IRS1; insulin receptor substrate 1 [KO:K16172]
100948398  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X2 [KO:K01116] [EC:3.1.4.11]
100948829  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
100951664  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
100952803  calmodulin-like [KO:K02183]
100956147  calmodulin-like [KO:K02183]
105887316  CALML6; calmodulin-like protein 6 [KO:K02183]
100942721  calmodulin-like [KO:K02183]
100941613  CALM3; calmodulin-3 [KO:K02183]
100964319  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
100946498  CALM2; calmodulin-2 [KO:K02183]
100966114  CALML5; calmodulin-like protein 5 [KO:K02183]
100948288  CALM1; calmodulin-1 [KO:K02183]
100941825  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
100955681  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X2 [KO:K04515] [EC:2.7.11.17]
100956846  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515] [EC:2.7.11.17]
100950655  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
100963188  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
100961758  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
100955860  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X2 [KO:K07293] [EC:3.1.3.48]
100953987  MATK; megakaryocyte-associated tyrosine-protein kinase [KO:K08888] [EC:2.7.10.2]
100948280  NGFR; tumor necrosis factor receptor superfamily member 16 isoform X2 [KO:K02583]
100942423  ARHGDIB; rho GDP-dissociation inhibitor 2 [KO:K12462]
100951332  ARHGDIA; rho GDP-dissociation inhibitor 1 [KO:K12462]
100964881  ARHGDIG; rho GDP-dissociation inhibitor 3 [KO:K12462]
100954771  RHOA; transforming protein RhoA [KO:K04513]
100947706  cell division control protein 42 homolog [KO:K04393]
100950992  CDC42; cell division control protein 42 homolog [KO:K04393]
100951369  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
100957675  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
100943232  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
100966900  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X4 [KO:K04431] [EC:2.7.12.2]
100957169  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
100967053  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100960275  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
100965098  JUN; transcription factor AP-1 [KO:K04448]
100963622  TP53; cellular tumor antigen p53 [KO:K04451]
100957285  BAX; apoptosis regulator BAX [KO:K02159]
100941774  TP73; tumor protein p73 isoform X1 [KO:K10148]
100945817  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
100949264  ZNF274; neurotrophin receptor-interacting factor homolog isoform X1 [KO:K12458]
100941197  PRDM4; PR domain zinc finger protein 4 [KO:K12463] [EC:2.1.1.-]
100949004  MAGED1; melanoma-associated antigen D1 [KO:K12464]
100962750  BEX3; protein BEX3 isoform X1 [KO:K12465]
100959168  YWHAE; 14-3-3 protein epsilon [KO:K06630]
100954549  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X3 [KO:K08846] [EC:2.7.11.1]
100951843  IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
100966956  IRAK2; interleukin-1 receptor-associated kinase-like 2 [KO:K04731] [EC:2.7.11.1]
100949174  IRAK3; interleukin-1 receptor-associated kinase 3 [KO:K04732] [EC:2.7.11.1]
100956612  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
100946157  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
100947840  SORT1; sortilin isoform X2 [KO:K12388]
100958952  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
oga04010  MAPK signaling pathway
oga04120  Ubiquitin mediated proteolysis
oga04210  Apoptosis
oga04720  Long-term potentiation
oga04810  Regulation of actin cytoskeleton
KO pathway
ko04722   
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