KEGG   PATHWAY: hsa04722Help
Entry
hsa04722                    Pathway                                

Name
Neurotrophin signaling pathway - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
hsa04722  Neurotrophin signaling pathway
hsa04722

Ortholog table
Disease
H00078  Frontotemporal lobar degeneration
H00265  Hereditary sensory and autonomic neuropathy
H00408  Type 1 diabetes mellitus
H00681  Acne inversa
H00916  Congenital central hypoventilation syndrome
H01007  Choroid plexus papilloma
H01018  Metachondromatosis
H01836  Congenital pain insensitivity with anhidrosis
Drug
D08869  Begacestat (USAN/INN)
D09010  Tarenflurbil (USAN/INN)
D09377  Semagacestat (USAN/INN)
D09869  Avagacestat (USAN)
D09907  Fulranumab (USAN/INN)
D10334  Rebastinib (USAN)
D10399  Rebastinib Tosylate (USAN)
D11137  Larotrectinib (USAN/INN)
D11138  Larotrectinib sulfate (USAN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
4803  NGF; nerve growth factor [KO:K02582]
627  BDNF; brain derived neurotrophic factor [KO:K04355]
4909  NTF4; neurotrophin 4 [KO:K12457]
4908  NTF3; neurotrophin 3 [KO:K04356]
4914  NTRK1; neurotrophic receptor tyrosine kinase 1 [KO:K03176] [EC:2.7.10.1]
4915  NTRK2; neurotrophic receptor tyrosine kinase 2 [KO:K04360] [EC:2.7.10.1]
4916  NTRK3; neurotrophic receptor tyrosine kinase 3 [KO:K05101] [EC:2.7.10.1]
10603  SH2B2; SH2B adaptor protein 2 [KO:K07193]
25970  SH2B1; SH2B adaptor protein 1 [KO:K12459]
10019  SH2B3; SH2B adaptor protein 3 [KO:K12459]
2885  GRB2; growth factor receptor bound protein 2 [KO:K04364]
6654  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
6655  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
3265  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
3845  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
4893  NRAS; NRAS proto-oncogene, GTPase [KO:K07828]
5894  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
673  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
5604  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
5605  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
5594  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
6197  RPS6KA3; ribosomal protein S6 kinase A3 [KO:K04373] [EC:2.7.11.1]
6195  RPS6KA1; ribosomal protein S6 kinase A1 [KO:K04373] [EC:2.7.11.1]
6196  RPS6KA2; ribosomal protein S6 kinase A2 [KO:K04373] [EC:2.7.11.1]
27330  RPS6KA6; ribosomal protein S6 kinase A6 [KO:K04373] [EC:2.7.11.1]
9252  RPS6KA5; ribosomal protein S6 kinase A5 [KO:K04445] [EC:2.7.11.1]
468  ATF4; activating transcription factor 4 [KO:K04374]
596  BCL2; BCL2, apoptosis regulator [KO:K02161]
57498  KIDINS220; kinase D interacting substrate 220 [KO:K12460]
10818  FRS2; fibroblast growth factor receptor substrate 2 [KO:K12461]
1398  CRK; CRK proto-oncogene, adaptor protein [KO:K04438]
1399  CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438]
2889  RAPGEF1; Rap guanine nucleotide exchange factor 1 [KO:K06277]
5906  RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
5908  RAP1B; RAP1B, member of RAS oncogene family [KO:K07836]
4215  MAP3K3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
5607  MAP2K5; mitogen-activated protein kinase kinase 5 [KO:K04463] [EC:2.7.12.2]
5598  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
5600  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
6300  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
5603  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
1432  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
9261  MAPKAPK2; mitogen-activated protein kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
6464  SHC1; SHC adaptor protein 1 [KO:K06279]
25759  SHC2; SHC adaptor protein 2 [KO:K17447]
53358  SHC3; SHC adaptor protein 3 [KO:K17448]
399694  SHC4; SHC adaptor protein 4 [KO:K17449]
2549  GAB1; GRB2 associated binding protein 1 [KO:K09593]
5295  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
5296  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
8503  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
5290  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
5293  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
5291  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
207  AKT1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
208  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
10000  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
4793  NFKBIB; NFKB inhibitor beta [KO:K02581]
4792  NFKBIA; NFKB inhibitor alpha [KO:K04734]
4794  NFKBIE; NFKB inhibitor epsilon [KO:K05872]
4790  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
5970  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
2309  FOXO3; forkhead box O3 [KO:K09408]
356  FASLG; Fas ligand [KO:K04389]
572  BAD; BCL2 associated agonist of cell death [KO:K02158]
2932  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
5170  PDPK1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
3667  IRS1; insulin receptor substrate 1 [KO:K16172]
5335  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
5336  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
5580  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
810  CALML3; calmodulin like 3 [KO:K02183]
805  CALM2; calmodulin 2 [KO:K02183]
808  CALM3; calmodulin 3 [KO:K02183]
801  CALM1; calmodulin 1 [KO:K02183]
163688  CALML6; calmodulin like 6 [KO:K02183]
51806  CALML5; calmodulin like 5 [KO:K02183]
91860  CALML4; calmodulin like 4 [KO:K02183]
815  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
817  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
816  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
818  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
814  CAMK4; calcium/calmodulin dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
25  ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
5781  PTPN11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
4145  MATK; megakaryocyte-associated tyrosine kinase [KO:K08888] [EC:2.7.10.2]
4804  NGFR; nerve growth factor receptor [KO:K02583]
397  ARHGDIB; Rho GDP dissociation inhibitor beta [KO:K12462]
396  ARHGDIA; Rho GDP dissociation inhibitor alpha [KO:K12462]
398  ARHGDIG; Rho GDP dissociation inhibitor gamma [KO:K12462]
387  RHOA; ras homolog family member A [KO:K04513]
998  CDC42; cell division cycle 42 [KO:K04393]
5879  RAC1; Rac family small GTPase 1 [KO:K04392]
4214  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
4217  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
5609  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
5599  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
3725  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
7157  TP53; tumor protein p53 [KO:K04451]
581  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
7161  TP73; tumor protein p73 [KO:K10148]
7189  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
10782  ZNF274; zinc finger protein 274 [KO:K12458]
11108  PRDM4; PR/SET domain 4 [KO:K12463]
9500  MAGED1; MAGE family member D1 [KO:K12464]
27018  BEX3; brain expressed X-linked 3 [KO:K12465]
7531  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
8767  RIPK2; receptor interacting serine/threonine kinase 2 [KO:K08846] [EC:2.7.11.1]
3654  IRAK1; interleukin 1 receptor associated kinase 1 [KO:K04730] [EC:2.7.11.1]
3656  IRAK2; interleukin 1 receptor associated kinase 2 [KO:K04731] [EC:2.7.11.1]
11213  IRAK3; interleukin 1 receptor associated kinase 3 [KO:K04732] [EC:2.7.11.1]
51135  IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1]
3551  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
6272  SORT1; sortilin 1 [KO:K12388]
5663  PSEN1; presenilin 1 [KO:K04505] [EC:3.4.23.-]
5664  PSEN2; presenilin 2 [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
  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
  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
  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
  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
  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
  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
  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
  Authors
Zampieri N, Chao MV
  Title
Mechanisms of neurotrophin receptor signalling.
  Journal
Biochem Soc Trans 34:607-11 (2006)
DOI:10.1042/BST0340607
Reference
  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
  Authors
Yano H, Chao MV
  Title
Neurotrophin receptor structure and interactions.
  Journal
Pharm Acta Helv 74:253-60 (2000)
Reference
  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
  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
KO pathway
ko04722   

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