KEGG   PATHWAY: rno04722
Entry
rno04722                    Pathway                                
Name
Neurotrophin signaling pathway - Rattus norvegicus (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
rno04722  Neurotrophin signaling pathway
rno04722

Organism
Rattus norvegicus (rat) [GN:rno]
Gene
114203  Sh2b2; SH2B adapter protein 2 [KO:K07193]
114486  Braf; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
114509  Mapk7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
114858  Shc3; SHC-transforming protein 3 [KO:K17448]
116478  Kidins220; kinase D-interacting substrate of 220 kDa [KO:K12460]
116554  Mapk8; mitogen-activated protein kinase 8 [KO:K04440] [EC:2.7.11.24]
116590  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116667  Map3k1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
117089  Bex3; protein BEX3 isoform 1 [KO:K12465]
117269  Rps6ka2; ribosomal protein S6 kinase alpha-2 [KO:K04373] [EC:2.7.11.1]
117273  Rhoa; transforming protein RhoA [KO:K04513]
134484121  [KO:K00922] [EC:2.7.1.153]
170538  Prkcd; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
170820  Prdm4; PR domain zinc finger protein 4 [KO:K12463] [EC:2.1.1.-]
170851  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
170911  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
171140  Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
171337  Rap1b; ras-related protein Rap-1b precursor [KO:K07836]
24185  Akt1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
24224  Bcl2; apoptosis regulator Bcl-2 [KO:K02161]
24225  Bdnf; brain-derived neurotrophic factor isoform 3 preproprotein [KO:K04355]
24242  Calm1; calmodulin-1 [KO:K02183]
24244  Calm3; calmodulin-3 [KO:K02183]
24245  Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform 2 [KO:K04515] [EC:2.7.11.17]
24246  Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
24516  Jun; transcription factor Jun [KO:K04448]
24525  Kras; GTPase KRas [KO:K07827]
24596  Ngfr; tumor necrosis factor receptor superfamily member 16 precursor [KO:K02583]
24605  Nras; GTPase NRas [KO:K07828]
24703  Raf1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
24842  Tp53; cellular tumor antigen p53 [KO:K04451]
24887  Bax; apoptosis regulator BAX [KO:K02159]
25050  Camk4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
25054  Ntrk2; BDNF/NT-3 growth factors receptor isoform 1 precursor [KO:K04360] [EC:2.7.10.1]
25233  Akt2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
25272  Mapk10; mitogen-activated protein kinase 10 isoform 2 [KO:K04440] [EC:2.7.11.24]
25385  Faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
25400  Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
25467  Irs1; insulin receptor substrate 1 [KO:K16172]
25493  Nfkbia; NF-kappa-B inhibitor alpha [KO:K04734]
25513  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
25622  Ptpn11; tyrosine-protein phosphatase non-receptor type 11 isoform 2 [KO:K07293] [EC:3.1.3.48]
25730  Ntf4; neurotrophin-4 precursor [KO:K12457]
25738  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
287942  Crkl; crk-like protein [KO:K04438]
289014  Mapkapk2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
29192  Psen1; presenilin-1 [KO:K04505] [EC:3.4.23.-]
29337  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
293621  Hras; GTPase HRas [KO:K02833]
29414  Akt3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
294515  Foxo3; forkhead box protein O3 [KO:K09408]
29513  Mapk13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
295347  Rap1a; ras-related protein Rap-1A [KO:K04353]
29568  Map2k5; dual specificity mitogen-activated protein kinase kinase 5 isoform a [KO:K04463] [EC:2.7.12.2]
29613  Ntrk3; NT-3 growth factor receptor isoform 1 precursor [KO:K05101] [EC:2.7.10.1]
297173  RSA-14-44; ras homolog gene family, member A [KO:K04513]
29741  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
29753  Ywhae; 14-3-3 protein epsilon [KO:K06630]
300177  Irak4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
303604  Map3k3; mitogen-activated protein kinase kinase kinase 3 [KO:K04421] [EC:2.7.11.25]
307100  Calml3; calmodulin-like protein 3 [KO:K02183]
308362  Zfp110; neurotrophin receptor-interacting factor 1 [KO:K12458]
309165  Rela; transcription factor p65 [KO:K04735]
310738  Ngf; beta-nerve growth factor precursor [KO:K02582]
311245  Traf6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
311860  Abl1; tyrosine-protein kinase ABL1 [KO:K06619] [EC:2.7.10.2]
313845  Sos1; son of sevenless homolog 1 [KO:K03099]
314384  Rps6ka5; ribosomal protein S6 kinase alpha-5 [KO:K04445] [EC:2.7.11.1]
314612  Shc2; SHC-transforming protein 2 [KO:K17447]
314850  Frs2; fibroblast growth factor receptor substrate 2 [KO:K12461]
314870  Irak3; interleukin-1 receptor-associated kinase 3 [KO:K04732] [EC:2.7.11.1]
316241  Nfkbie; NF-kappa-B inhibitor epsilon [KO:K05872]
317203  Rps6ka6; ribosomal protein S6 kinase alpha-6 [KO:K04373] [EC:2.7.11.1]
360500  Arhgdig; rho GDP-dissociation inhibitor 3 [KO:K12462]
360678  Arhgdia; rho GDP-dissociation inhibitor 1 [KO:K12462]
361388  Gab1; GRB2-associated-binding protein 1 [KO:K09593]
362418  Irak2; interleukin-1 receptor-associated kinase-like 2 [KO:K04731] [EC:2.7.11.1]
362456  Arhgdib; rho GDP-dissociation inhibitor 2 [KO:K12462]
362491  Ripk2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
362675  Tp73; tumor protein p73 [KO:K10148]
363520  Irak1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
363855  Map2k7; dual specificity mitogen-activated protein kinase kinase 7 isoform 1 [KO:K04431] [EC:2.7.12.2]
363875  Rac1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
364774  Calml5; calmodulin-like protein 5 [KO:K02183]
365057  Map3k5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
366508  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
367149  Bax-ps1; apoptosis regulator BAX-like [KO:K02159]
367858  Hrasl1; HRas proto-oncogene, GTPase like 1 [KO:K02833]
501560  Rps6ka3; ribosomal protein S6 kinase alpha-3 [KO:K04373] [EC:2.7.11.1]
50658  Mapk9; mitogen-activated protein kinase 9 isoform 2 [KO:K04440] [EC:2.7.11.24]
50663  Calm2; calmodulin-2 [KO:K02183]
50689  Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
54245  Crk; adapter molecule crk [KO:K04438]
58838  Sh2b3; SH2B adapter protein 3 [KO:K12459]
58960  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
59109  Ntrk1; high affinity nerve growth factor receptor precursor [KO:K03176] [EC:2.7.10.1]
60352  Mapk12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
60450  Matk; megakaryocyte-associated tyrosine-protein kinase [KO:K08888] [EC:2.7.10.2]
60664  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
63881  Rapgef1; rap guanine nucleotide exchange factor 1 isoform X25 [KO:K06277]
64465  Cdc42; cell division control protein 42 homolog [KO:K04393]
64639  Bad; bcl2-associated agonist of cell death [KO:K02158]
679845  Shc4; SHC-transforming protein 4 [KO:K17449]
681314  [KO:K02159]
689314  Mapk11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
691455  Calml4; calmodulin-like protein 4 [KO:K02183]
79255  Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
81504  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
81525  Nfkbib; NF-kappa-B inhibitor beta [KO:K02581]
81649  Mapk14; mitogen-activated protein kinase 14 [KO:K04441] [EC:2.7.11.24]
81736  Nfkb1; nuclear factor NF-kappa-B p105 subunit isoform 2 [KO:K02580]
81737  Ntf3; neurotrophin-3 isoform 3 precursor [KO:K04356]
81745  Pdpk1; 3-phosphoinositide-dependent protein kinase 1 [KO:K06276] [EC:2.7.11.1]
81751  Psen2; presenilin-2 [KO:K04522] [EC:3.4.23.-]
81771  Rps6ka1; ribosomal protein S6 kinase alpha-1 [KO:K04373] [EC:2.7.11.1]
83576  Sort1; sortilin precursor [KO:K12388]
84027  Gsk3b; glycogen synthase kinase-3 beta [KO:K03083] [EC:2.7.11.26]
84351  Ikbkb; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
84469  Maged1; melanoma-associated antigen D1 [KO:K12464]
85243  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
85384  Sos2; son of sevenless homolog 2 [KO:K03099]
85385  Shc1; SHC-transforming protein 1 isoform b [KO:K06279]
89817  Sh2b1; SH2B adapter protein 1 isoform 1 [KO:K12459]
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
rno04010  MAPK signaling pathway
rno04120  Ubiquitin mediated proteolysis
rno04210  Apoptosis
rno04720  Long-term potentiation
rno04810  Regulation of actin cytoskeleton
KO pathway
ko04722   

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