KEGG   PATHWAY: ptg04722
Entry
ptg04722                    Pathway                                
Name
Neurotrophin signaling pathway - Panthera tigris altaica (Amur tiger)
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
ptg04722  Neurotrophin signaling pathway
ptg04722

Organism
Panthera tigris altaica (Amur tiger) [GN:ptg]
Gene
102961057  NGF; nerve growth factor [KO:K02582]
102958723  BDNF; brain derived neurotrophic factor [KO:K04355]
102951714  NTF4; neurotrophin 4 [KO:K12457]
102966385  NTF3; neurotrophin 3 [KO:K04356]
102950315  NTRK2; neurotrophic receptor tyrosine kinase 2 [KO:K04360] [EC:2.7.10.1]
102965762  NTRK3; neurotrophic receptor tyrosine kinase 3 [KO:K05101] [EC:2.7.10.1]
102949441  SH2B2; SH2B adaptor protein 2 [KO:K07193]
102955506  SH2B3; SH2B adaptor protein 3 [KO:K12459]
102971307  SH2B1; SH2B adaptor protein 1 [KO:K12459]
102970459  GRB2; growth factor receptor bound protein 2 [KO:K04364]
102949403  SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
102950748  SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
102952119  HRAS; HRas proto-oncogene, GTPase [KO:K02833]
102957350  KRAS; KRAS proto-oncogene, GTPase [KO:K07827]
102952980  NRAS; neuroblastoma RAS viral oncogene homolog [KO:K07828]
102955852  RAF1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
102951082  BRAF; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
102969757  MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
102956808  MAP2K2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
102964841  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
102960964  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
102959548  RPS6KA1; ribosomal protein S6 kinase A1 [KO:K04373] [EC:2.7.11.1]
102964555  RPS6KA3; ribosomal protein S6 kinase A3 [KO:K04373] [EC:2.7.11.1]
102954716  RPS6KA2; ribosomal protein S6 kinase A2 [KO:K04373] [EC:2.7.11.1]
102959403  RPS6KA6; ribosomal protein S6 kinase A6 [KO:K04373] [EC:2.7.11.1]
102952316  RPS6KA5; ribosomal protein S6 kinase A5 [KO:K04445] [EC:2.7.11.1]
102950077  ATF4; activating transcription factor 4 [KO:K04374]
102953487  BCL2; BCL2, apoptosis regulator [KO:K02161]
102972641  KIDINS220; kinase D interacting substrate 220 [KO:K12460]
102968761  FRS2; fibroblast growth factor receptor substrate 2 [KO:K12461]
102957241  CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438]
102956621  CRK; CRK proto-oncogene, adaptor protein [KO:K04438]
102962616  RAPGEF1; Rap guanine nucleotide exchange factor 1 [KO:K06277]
102963243  RAP1A; RAP1A, member of RAS oncogene family [KO:K04353]
102965011  RAP1B; RAP1B, member of RAS oncogene family [KO:K07836]
102966576  MAP3K3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
102949008  MAP2K5; mitogen-activated protein kinase kinase 5 [KO:K04463] [EC:2.7.12.2]
102964803  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
102968191  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
102960306  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
102960590  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
102968482  MAPK14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
102961644  MAPKAPK2; mitogen-activated protein kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
102949026  SHC1; SHC adaptor protein 1 [KO:K06279]
102954336  SHC2; SHC adaptor protein 2 [KO:K17447]
102965813  SHC3; SHC adaptor protein 3 [KO:K17448]
102955115  SHC4; SHC adaptor protein 4 [KO:K17449]
102959239  GAB1; GRB2 associated binding protein 1 [KO:K09593]
102949853  PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
102952993  PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
102967709  PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
102953082  PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
102965070  PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
102972487  PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
102952603  AKT3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
102954757  AKT2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
102948803  NFKBIB; NFKB inhibitor beta [KO:K02581]
102956127  NFKBIA; NFKB inhibitor alpha [KO:K04734]
102956483  NFKBIE; NFKB inhibitor epsilon [KO:K05872]
102964232  NFKB1; nuclear factor kappa B subunit 1 [KO:K02580]
102951132  RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735]
102961930  FOXO3; forkhead box O3 [KO:K09408]
102953222  FASLG; Fas ligand [KO:K04389]
102956027  BAD; BCL2 associated agonist of cell death [KO:K02158]
102961382  GSK3B; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
102960424  PDPK1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
102965599  IRS1; insulin receptor substrate 1 [KO:K16172]
102952137  PLCG1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
102963653  PLCG2; phospholipase C gamma 2 [KO:K05859] [EC:3.1.4.11]
102959855  PRKCD; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
102953457  CALM3; calmodulin 3 [KO:K02183]
102963939  calmodulin-like [KO:K02183]
102964234  CALML3; calmodulin-like protein 3 [KO:K02183]
102954552  CALM2; calmodulin 2 [KO:K02183]
102960923  calmodulin-like [KO:K02183]
102950842  CALML6; calmodulin like 6 [KO:K02183]
102951822  CALM1; calmodulin 1 [KO:K02183]
102971520  calmodulin-alpha-like [KO:K02183]
102950182  CALML4; calmodulin like 4 [KO:K02183]
102964851  CAMK2B; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
102966494  CAMK2A; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
102957556  CAMK2G; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
102950197  CAMK2D; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
102954895  CAMK4; calcium/calmodulin dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
102949569  ABL1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
102951653  PTPN11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
102954137  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
102958221  MATK; megakaryocyte-associated tyrosine kinase [KO:K08888] [EC:2.7.10.2]
102953999  NGFR; nerve growth factor receptor [KO:K02583]
102972157  ARHGDIA; Rho GDP dissociation inhibitor alpha [KO:K12462]
102961767  ARHGDIB; Rho GDP dissociation inhibitor beta [KO:K12462]
102950718  ARHGDIG; Rho GDP dissociation inhibitor gamma [KO:K12462]
102952555  RHOA; ras homolog family member A [KO:K04513]
102973021  CDC42; cell division cycle 42 [KO:K04393]
102968561  RAC1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
102971191  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
102960317  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
102949140  MAP2K7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
102959159  MAPK10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
102950880  MAPK8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
102963096  MAPK9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
102958666  JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
102962571  TP53; tumor protein p53 [KO:K04451]
102949153  BAX; BCL2 associated X, apoptosis regulator [KO:K02159]
102960157  TRAF6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
102967173  ZNF274; zinc finger protein 274 [KO:K12458]
102951343  PRDM4; PR/SET domain 4 [KO:K12463] [EC:2.1.1.-]
102950737  MAGED1; MAGE family member D1 [KO:K12464]
102960952  protein BEX3 [KO:K12465]
102960323  14-3-3 protein epsilon [KO:K06630]
102970295  YWHAE; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
102957311  RIPK2; receptor interacting serine/threonine kinase 2 [KO:K08846] [EC:2.7.11.1]
102964669  IRAK2; interleukin 1 receptor associated kinase 2 [KO:K04731] [EC:2.7.11.1]
102953004  IRAK3; interleukin 1 receptor associated kinase 3 [KO:K04732] [EC:2.7.11.1]
102962570  IRAK4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1]
102963734  IKBKB; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
102954219  SORT1; sortilin 1 [KO:K12388]
102966511  PSEN1; presenilin 1 [KO:K04505] [EC:3.4.23.-]
102972248  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
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
ptg04010  MAPK signaling pathway
ptg04120  Ubiquitin mediated proteolysis
ptg04210  Apoptosis
ptg04720  Long-term potentiation
ptg04810  Regulation of actin cytoskeleton
KO pathway
ko04722   
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