KEGG   PATHWAY: ko04722
Entry
ko04722                     Pathway                                
Name
Neurotrophin signaling pathway
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
ko04722  Neurotrophin signaling pathway
ko04722

Orthology
K00922  PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153]
K01116  PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11]
K02158  BAD; Bcl-2-antagonist of cell death
K02159  BAX; apoptosis regulator BAX
K02161  BCL2; apoptosis regulator Bcl-2
K02183  CALM; calmodulin
K02580  NFKB1; nuclear factor NF-kappa-B p105 subunit
K02581  NFKBIB; NF-kappa-B inhibitor beta
K02582  NGFB; nerve growth factor, beta
K02583  NGFR, TNFRSF16, CD271; tumor necrosis factor receptor superfamily member 16
K02649  PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K02833  HRAS; GTPase HRas
K03083  GSK3B; glycogen synthase kinase 3 beta [EC:2.7.11.26]
K03099  SOS; son of sevenless
K03175  TRAF6; TNF receptor-associated factor 6 [EC:2.3.2.27]
K03176  NTRK1, TRKA; neurotrophic tyrosine kinase receptor type 1 [EC:2.7.10.1]
K04353  RAP1A; Ras-related protein Rap-1A
K04355  BDNF; brain-derived neurotrophic factor
K04356  NTF3; neurotrophin 3
K04360  NTRK2, TRKB; neurotrophic tyrosine kinase receptor type 2 [EC:2.7.10.1]
K04364  GRB2; growth factor receptor-bound protein 2
K04365  BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04366  RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1]
K04368  MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2]
K04369  MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2]
K04371  ERK, MAPK1_3; mitogen-activated protein kinase 1/3 [EC:2.7.11.24]
K04373  RPS6KA; ribosomal protein S6 kinase alpha-1/2/3/6 [EC:2.7.11.1]
K04374  ATF4, CREB2; cyclic AMP-dependent transcription factor ATF-4
K04389  TNFSF6, FASL, CD178; tumor necrosis factor ligand superfamily member 6
K04392  RAC1; Ras-related C3 botulinum toxin substrate 1
K04393  CDC42; cell division control protein 42
K04416  MAP3K1, MEKK1; mitogen-activated protein kinase kinase kinase 1 [EC:2.7.11.25]
K04421  MAP3K3, MEKK3; mitogen-activated protein kinase kinase kinase 3 [EC:2.7.11.25]
K04426  MAP3K5, ASK1; mitogen-activated protein kinase kinase kinase 5 [EC:2.7.11.25]
K04431  MAP2K7, MKK7; mitogen-activated protein kinase kinase 7 [EC:2.7.12.2]
K04438  CRK, CRKII; C-crk adapter molecule crk
K04440  JNK; mitogen-activated protein kinase 8/9/10 (c-Jun N-terminal kinase) [EC:2.7.11.24]
K04441  P38; p38 MAP kinase [EC:2.7.11.24]
K04443  MAPKAPK2; mitogen-activated protein kinase-activated protein kinase 2 [EC:2.7.11.1]
K04445  RPS6KA5, MSK1; ribosomal protein S6 kinase alpha-5 [EC:2.7.11.1]
K04448  JUN; transcription factor AP-1
K04451  TP53, P53; tumor protein p53
K04456  AKT; RAC serine/threonine-protein kinase [EC:2.7.11.1]
K04463  MAP2K5, MEK5; mitogen-activated protein kinase kinase 5 [EC:2.7.12.2]
K04464  MAPK7; mitogen-activated protein kinase 7 [EC:2.7.11.24]
K04505  PSEN1, PS1; presenilin 1 [EC:3.4.23.-]
K04513  RHOA; Ras homolog gene family, member A
K04515  CAMK2; calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17]
K04522  PSEN2, PS2; presenilin 2 [EC:3.4.23.-]
K04730  IRAK1; interleukin-1 receptor-associated kinase 1 [EC:2.7.11.1]
K04731  IRAK2; interleukin-1 receptor-associated kinase 2 [EC:2.7.11.1]
K04732  IRAK3; interleukin-1 receptor-associated kinase 3 [EC:2.7.11.1]
K04733  IRAK4; interleukin-1 receptor-associated kinase 4 [EC:2.7.11.1]
K04734  NFKBIA; NF-kappa-B inhibitor alpha
K04735  RELA; transcription factor p65
K05101  NTRK3, TRKC; neurotrophic tyrosine kinase, receptor type 3 [EC:2.7.10.1]
K05859  PLCG2; phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11]
K05869  CAMK4; calcium/calmodulin-dependent protein kinase IV [EC:2.7.11.17]
K05872  NFKBIE; NF-kappa-B inhibitor epsilon
K06068  PRKCD; novel protein kinase C delta type [EC:2.7.11.13]
K06276  PDPK1; 3-phosphoinositide dependent protein kinase-1 [EC:2.7.11.1]
K06277  RAPGEF1, GRF2; Rap guanine nucleotide exchange factor 1
K06279  SHC1; SHC-transforming protein 1
K06619  ABL1; abelson tyrosine-protein kinase 1 [EC:2.7.10.2]
K06630  YWHAE; 14-3-3 protein epsilon
K07193  SH2B, APS; SH2B adapter protein 2
K07209  IKBKB, IKKB; inhibitor of nuclear factor kappa-B kinase subunit beta [EC:2.7.11.10]
K07293  PTPN11, SHP2; tyrosine-protein phosphatase non-receptor type 11 [EC:3.1.3.48]
K07827  KRAS, KRAS2; GTPase KRas
K07828  NRAS; GTPase NRas
K07836  RAP1B; Ras-related protein Rap-1B
K08846  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [EC:2.7.11.1]
K08888  MATK; megakaryocyte-associated tyrosine kinase [EC:2.7.10.2]
K09408  FOXO3; forkhead box protein O3
K09593  GAB1; GRB2-associated-binding protein 1
K10148  TP73; tumor protein p73
K12388  SORT1; sortilin
K12457  NTF4; neurotrophin 4
K12458  ZNF274; zinc finger protein 274
K12459  SH2B1_3; SH2B adaptor protein 1/3
K12460  KIDINS220, ARMS; ankyrin repeat-rich membrane spanning protein
K12461  FRS2; fibroblast growth factor receptor substrate 2
K12462  ARHGDI, RHOGDI; Rho GDP-dissociation inhibitor
K12463  PRDM4; PR domain zinc finger protein 4 [EC:2.1.1.-]
K12464  MAGED1, NRAGE; melanoma-associated antigen D1
K12465  NGFRAP1; nerve growth factor receptor-associated protein 1
K16172  IRS1; insulin receptor substrate 1
K17447  SHC2; SHC-transforming protein 2
K17448  SHC3; SHC-transforming protein 3
K17449  SHC4; SHC-transforming protein 4
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
ko04010  MAPK signaling pathway
ko04120  Ubiquitin mediated proteolysis
ko04210  Apoptosis
ko04720  Long-term potentiation
ko04810  Regulation of actin cytoskeleton

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