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
Neurotrophin signaling pathway
hsa04722

All organismsOrtholog table
Disease
H00078  
Frontotemporal lobar degeneration (FTLD)
H00265  
Hereditary sensory and autonomic neuropathy (HSAN)
H00408  
Type I diabetes mellitus
H00681  
Acne inversa
H00916  
Congenital central hypoventilation syndrome (CCHS)
H01007  
Choroid plexus papilloma
H01018  
Metachondromatosis
Drug
D08869  
Begacestat (USAN/INN)
D09010  
Tarenflurbil (USAN/INN)
D09377  
Semagacestat (USAN/INN)
D09387  
Tanezumab (USAN/INN)
D09869  
Avagacestat (USAN)
D09907  
Fulranumab (USAN/INN)
D10334  
Rebastinib (USAN)
D10399  
Rebastinib Tosylate (USAN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
4803  
NGF; nerve growth factor (beta polypeptide) [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 tyrosine kinase, receptor, type 1 [KO:K03176] [EC:2.7.10.1]
4915  
NTRK2; neurotrophic tyrosine kinase, receptor, type 2 [KO:K04360] [EC:2.7.10.1]
4916  
NTRK3; neurotrophic tyrosine kinase, receptor, type 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; son of sevenless homolog 1 (Drosophila) [KO:K03099]
6655  
SOS2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
3265  
HRAS; Harvey rat sarcoma viral oncogene homolog [KO:K02833]
3845  
KRAS; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
4893  
NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [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, 90kDa, polypeptide 3 [KO:K04373] [EC:2.7.11.1]
6195  
RPS6KA1; ribosomal protein S6 kinase, 90kDa, polypeptide 1 [KO:K04373] [EC:2.7.11.1]
6196  
RPS6KA2; ribosomal protein S6 kinase, 90kDa, polypeptide 2 [KO:K04373] [EC:2.7.11.1]
27330  
RPS6KA6; ribosomal protein S6 kinase, 90kDa, polypeptide 6 [KO:K04373] [EC:2.7.11.1]
9252  
RPS6KA5; ribosomal protein S6 kinase, 90kDa, polypeptide 5 [KO:K04445] [EC:2.7.11.1]
468  
ATF4; activating transcription factor 4 [KO:K04374]
596  
BCL2; B-cell CLL/lymphoma 2 [KO:K02161]
57498  
KIDINS220; kinase D-interacting substrate, 220kDa [KO:K12460]
10818  
FRS2; fibroblast growth factor receptor substrate 2 [KO:K12461]
1398  
CRK; v-crk avian sarcoma virus CT10 oncogene homolog [KO:K04438]
1399  
CRKL; v-crk avian sarcoma virus CT10 oncogene homolog-like [KO:K04438]
2889  
RAPGEF1; Rap guanine nucleotide exchange factor (GEF) 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 (Src homology 2 domain containing) transforming protein 1 [KO:K06279]
25759  
SHC2; SHC (Src homology 2 domain containing) transforming protein 2 [KO:K17447]
53358  
SHC3; SHC (Src homology 2 domain containing) transforming protein 3 [KO:K17448]
399694  
SHC4; SHC (Src homology 2 domain containing) family, member 4 [KO:K17449]
2549  
GAB1; GRB2-associated binding protein 1 [KO:K09593]
5295  
PIK3R1; phosphoinositide-3-kinase, regulatory subunit 1 (alpha) [KO:K02649]
23533  
PIK3R5; phosphoinositide-3-kinase, regulatory subunit 5 [KO:K02649]
5296  
PIK3R2; phosphoinositide-3-kinase, regulatory subunit 2 (beta) [KO:K02649]
8503  
PIK3R3; phosphoinositide-3-kinase, regulatory subunit 3 (gamma) [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]
5294  
PIK3CG; phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma [KO:K00922] [EC:2.7.1.153]
207  
AKT1; v-akt murine thymoma viral oncogene homolog 1 [KO:K04456] [EC:2.7.11.1]
208  
AKT2; v-akt murine thymoma viral oncogene homolog 2 [KO:K04456] [EC:2.7.11.1]
10000  
AKT3; v-akt murine thymoma viral oncogene homolog 3 [KO:K04456] [EC:2.7.11.1]
4793  
NFKBIB; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, beta [KO:K02581]
4792  
NFKBIA; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha [KO:K04734]
4794  
NFKBIE; nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon [KO:K05872]
4790  
NFKB1; nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [KO:K02580]
5970  
RELA; v-rel avian reticuloendotheliosis viral oncogene homolog A [KO:K04735]
2309  
FOXO3; forkhead box O3 [KO:K09408]
356  
FASLG; Fas ligand (TNF superfamily, member 6) [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 (phosphatidylinositol-specific) [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 (phosphorylase kinase, delta) [KO:K02183]
808  
CALM3; calmodulin 3 (phosphorylase kinase, delta) [KO:K02183]
801  
CALM1; calmodulin 1 (phosphorylase kinase, delta) [KO:K02183]
163688  
CALML6; calmodulin-like 6 [KO:K02183]
51806  
CALML5; calmodulin-like 5 [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 (GDI) beta [KO:K12462]
396  
ARHGDIA; Rho GDP dissociation inhibitor (GDI) alpha [KO:K12462]
398  
ARHGDIG; Rho GDP dissociation inhibitor (GDI) gamma [KO:K12462]
387  
RHOA; ras homolog family member A [KO:K04513]
998  
CDC42; cell division cycle 42 [KO:K04393]
5879  
RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
4214  
MAP3K1; mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase [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 [KO:K04448]
7157  
TP53; tumor protein p53 [KO:K04451]
581  
BAX; BCL2-associated X protein [KO:K02159]
7161  
TP73; tumor protein p73 [KO:K10148]
7189  
TRAF6; TNF receptor-associated factor 6, E3 ubiquitin protein ligase [KO:K03175]
10782  
ZNF274; zinc finger protein 274 [KO:K12458]
11108  
PRDM4; PR domain containing 4 [KO:K12463]
9500  
MAGED1; melanoma antigen family D, 1 [KO:K12464]
27018  
NGFRAP1; nerve growth factor receptor (TNFRSF16) associated protein 1 [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 kappa light polypeptide gene enhancer in B-cells, kinase 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)
Reference
  Authors
Patapoutian A, Reichardt LF
  Title
Trk receptors: mediators of neurotrophin action.
  Journal
Curr Opin Neurobiol 11:272-80 (2001)
Reference
  Authors
Arevalo JC, Wu SH
  Title
Neurotrophin signaling: many exciting surprises!
  Journal
Cell Mol Life Sci 63:1523-37 (2006)
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)
Reference
  Authors
Miller FD, Kaplan DR
  Title
Neurotrophin signalling pathways regulating neuronal apoptosis.
  Journal
Cell Mol Life Sci 58:1045-53 (2001)
Reference
  Authors
Kaplan DR, Miller FD
  Title
Neurotrophin signal transduction in the nervous system.
  Journal
Curr Opin Neurobiol 10:381-91 (2000)
Reference
  Authors
Reichardt LF
  Title
Neurotrophin-regulated signalling pathways.
  Journal
Philos Trans R Soc Lond B Biol Sci 361:1545-64 (2006)
Reference
  Authors
Zampieri N, Chao MV
  Title
Mechanisms of neurotrophin receptor signalling.
  Journal
Biochem Soc Trans 34:607-11 (2006)
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)
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)
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)
KO pathway
 

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