KEGG   PATHWAY: ngi04722
Entry
ngi04722                    Pathway                                
Name
Neurotrophin signaling pathway - Nannospalax galili (Upper Galilee mountains blind mole rat)
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
ngi04722  Neurotrophin signaling pathway
ngi04722

Organism
Nannospalax galili (Upper Galilee mountains blind mole rat) [GN:ngi]
Gene
103734944  Ngf; nerve growth factor [KO:K02582]
103748489  Bdnf; brain derived neurotrophic factor [KO:K04355]
103743645  Ntf4; neurotrophin 4 [KO:K12457]
103727536  Ntf3; neurotrophin 3 [KO:K04356]
103750263  Ntrk1; neurotrophic receptor tyrosine kinase 1 [KO:K03176] [EC:2.7.10.1]
103747093  Ntrk2; neurotrophic receptor tyrosine kinase 2 [KO:K04360] [EC:2.7.10.1]
103749925  Ntrk3; neurotrophic receptor tyrosine kinase 3 [KO:K05101] [EC:2.7.10.1]
103733485  Sh2b2; SH2B adaptor protein 2 [KO:K07193]
103745577  Sh2b3; SH2B adaptor protein 3 [KO:K12459]
103726405  Sh2b1; SH2B adaptor protein 1 [KO:K12459]
103732729  Grb2; growth factor receptor bound protein 2 [KO:K04364]
103743944  Sos1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099]
103731514  Sos2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099]
103751075  Hras; HRas proto-oncogene, GTPase [KO:K02833]
103736717  Kras; KRAS proto-oncogene, GTPase [KO:K07827]
103734938  Nras; neuroblastoma RAS viral oncogene homolog [KO:K07828]
103751450  Raf1; Raf-1 proto-oncogene, serine/threonine kinase [KO:K04366] [EC:2.7.11.1]
103726107  Braf; B-Raf proto-oncogene, serine/threonine kinase [KO:K04365] [EC:2.7.11.1]
103736801  Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103737276  Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103741442  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103726390  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103736232  Rps6ka3; ribosomal protein S6 kinase A3 [KO:K04373] [EC:2.7.11.1]
103735725  Rps6ka2; ribosomal protein S6 kinase A2 [KO:K04373] [EC:2.7.11.1]
103737117  Rps6ka1; ribosomal protein S6 kinase A1 [KO:K04373] [EC:2.7.11.1]
103725267  Rps6ka6; ribosomal protein S6 kinase A6 [KO:K04373] [EC:2.7.11.1]
103724612  Rps6ka5; ribosomal protein S6 kinase A5 [KO:K04445] [EC:2.7.11.1]
103748563  Atf4; activating transcription factor 4 [KO:K04374]
103740099  Bcl2; BCL2, apoptosis regulator [KO:K02161]
103747635  Kidins220; kinase D interacting substrate 220 [KO:K12460]
103726237  Frs2; fibroblast growth factor receptor substrate 2 [KO:K12461]
103741458  Crkl; CRK like proto-oncogene, adaptor protein [KO:K04438]
103730505  Crk; CRK proto-oncogene, adaptor protein [KO:K04438]
103742879  Rapgef1; Rap guanine nucleotide exchange factor 1 [KO:K06277]
103734905  Rap1a; RAP1A, member of RAS oncogene family [KO:K04353]
103745076  Rap1b; RAP1B, member of RAS oncogene family [KO:K07836]
103744757  Map3k3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
103736811  Map2k5; mitogen-activated protein kinase kinase 5 [KO:K04463] [EC:2.7.12.2]
103728439  Mapk7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
103739660  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
103739659  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103735473  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103735474  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103725934  Mapkapk2; mitogen-activated protein kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
103751254  Shc1; SHC adaptor protein 1 [KO:K06279]
103737407  Shc2; SHC adaptor protein 2 [KO:K17447]
103726215  Shc3; SHC adaptor protein 3 [KO:K17448]
103733036  Shc4; SHC adaptor protein 4 [KO:K17449]
103742387  Gab1; GRB2 associated binding protein 1 [KO:K09593]
103738715  Pik3r1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649]
103726879  Pik3r2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649]
103730305  Pik3r3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649]
103738596  Pik3ca; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153]
103733121  Pik3cd; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153]
103742946  Pik3cb; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153]
103746884  Akt3; AKT serine/threonine kinase 3 [KO:K04456] [EC:2.7.11.1]
103750757  Akt2; AKT serine/threonine kinase 2 [KO:K04456] [EC:2.7.11.1]
103752536  Akt1; AKT serine/threonine kinase 1 [KO:K04456] [EC:2.7.11.1]
103750726  Nfkbib; NFKB inhibitor beta [KO:K02581]
103734016  Nfkbia; NFKB inhibitor alpha [KO:K04734]
103730765  Nfkbie; NFKB inhibitor epsilon [KO:K05872]
103728077  Nfkb1; nuclear factor kappa B subunit 1 [KO:K02580]
103724994  Rela; RELA proto-oncogene, NF-kB subunit [KO:K04735]
103749566  Foxo3; forkhead box O3 [KO:K09408]
103740694  Faslg; Fas ligand [KO:K04389]
103738795  Bad; BCL2 associated agonist of cell death [KO:K02158]
103741948  Gsk3b; glycogen synthase kinase 3 beta [KO:K03083] [EC:2.7.11.26]
103743959  Pdpk1; 3-phosphoinositide dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
103727788  Irs1; insulin receptor substrate 1 [KO:K16172]
103747244  Plcg1; phospholipase C gamma 1 [KO:K01116] [EC:3.1.4.11]
103748739  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
103725694  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2-like [KO:K05859] [EC:3.1.4.11]
103749021  Prkcd; protein kinase C delta [KO:K06068] [EC:2.7.11.13]
103737134  Calml3; calmodulin like 3 [KO:K02183]
103737133  Calml5; calmodulin like 5 [KO:K02183]
103749800  Calml6; calmodulin like 6 [KO:K02183]
103724616  Calm1; calmodulin 1 [KO:K02183]
103724738  Calm3; calmodulin 3 [KO:K02183]
103725745  Calm2; calmodulin 2 [KO:K02183]
103729208  calmodulin-alpha-like [KO:K02183]
103736816  Calml4; calmodulin like 4 [KO:K02183]
103736933  Camk2g; calcium/calmodulin dependent protein kinase II gamma [KO:K04515] [EC:2.7.11.17]
103734983  Camk2b; calcium/calmodulin dependent protein kinase II beta [KO:K04515] [EC:2.7.11.17]
103743264  Camk2d; calcium/calmodulin dependent protein kinase II delta [KO:K04515] [EC:2.7.11.17]
103747079  Camk2a; calcium/calmodulin dependent protein kinase II alpha [KO:K04515] [EC:2.7.11.17]
103752296  Camk4; calcium/calmodulin dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
103727721  Abl1; ABL proto-oncogene 1, non-receptor tyrosine kinase [KO:K06619] [EC:2.7.10.2]
103745559  Ptpn11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
103737266  Matk; megakaryocyte-associated tyrosine kinase [KO:K08888] [EC:2.7.10.2]
103738367  Ngfr; nerve growth factor receptor [KO:K02583]
103730243  Arhgdia; Rho GDP dissociation inhibitor alpha [KO:K12462]
103748221  Arhgdig; Rho GDP dissociation inhibitor gamma [KO:K12462]
103752313  Arhgdib; Rho GDP dissociation inhibitor beta [KO:K12462]
103743359  transforming protein RhoA-like [KO:K04513]
103750189  Rhoa; ras homolog family member A [KO:K04513]
103746394  Cdc42; cell division cycle 42 [KO:K04393]
103726484  Rac1; ras-related C3 botulinum toxin substrate 1 (rho family, small GTP binding protein Rac1) [KO:K04392]
103739909  Map3k1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
103724902  Map3k5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
103726522  Map2k7; mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
103735023  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
103748972  Mapk10; mitogen-activated protein kinase 10 [KO:K04440] [EC:2.7.11.24]
103749366  Mapk9; mitogen-activated protein kinase 9 [KO:K04440] [EC:2.7.11.24]
103737138  Jun; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448]
103752115  Tp53; tumor protein p53 [KO:K04451]
103743639  Bax; BCL2 associated X, apoptosis regulator [KO:K02159]
103749787  Tp73; tumor protein p73 [KO:K10148]
103749513  Traf6; TNF receptor associated factor 6 [KO:K03175] [EC:2.3.2.27]
103725519  Znf274; zinc finger protein 274 [KO:K12458]
103742115  Prdm4; PR/SET domain 4 [KO:K12463] [EC:2.1.1.-]
103745664  Maged1; MAGE family member D1 [KO:K12464]
103733505  Bex3; brain expressed X-linked 3 [KO:K12465]
103730504  Ywhae; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon [KO:K06630]
103729531  Ripk2; receptor interacting serine/threonine kinase 2 [KO:K08846] [EC:2.7.11.1]
103731212  Irak1; interleukin 1 receptor associated kinase 1 [KO:K04730] [EC:2.7.11.1]
103751434  Irak2; interleukin 1 receptor associated kinase 2 [KO:K04731] [EC:2.7.11.1]
103730812  Irak3; interleukin 1 receptor associated kinase 3 [KO:K04732] [EC:2.7.11.1]
103728592  Irak4; interleukin 1 receptor associated kinase 4 [KO:K04733] [EC:2.7.11.1]
103726621  Ikbkb; inhibitor of nuclear factor kappa B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103747872  Sort1; sortilin 1 [KO:K12388]
103747390  Psen1; presenilin 1 [KO:K04505] [EC:3.4.23.-]
103725095  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
ngi04010  MAPK signaling pathway
ngi04120  Ubiquitin mediated proteolysis
ngi04210  Apoptosis
ngi04720  Long-term potentiation
ngi04810  Regulation of actin cytoskeleton
KO pathway
ko04722   
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