KEGG   PATHWAY: umr04722
Entry
umr04722                    Pathway                                
Name
Neurotrophin signaling pathway - Ursus maritimus (polar bear)
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
umr04722  Neurotrophin signaling pathway
umr04722

Organism
Ursus maritimus (polar bear) [GN:umr]
Gene
103669449  NGF; beta-nerve growth factor [KO:K02582]
103659367  BDNF; brain-derived neurotrophic factor [KO:K04355]
103657113  NTF4; LOW QUALITY PROTEIN: neurotrophin-4 [KO:K12457]
103656210  NTF3; neurotrophin-3 isoform X1 [KO:K04356]
103667631  NTRK2; BDNF/NT-3 growth factors receptor [KO:K04360] [EC:2.7.10.1]
103660166  NTRK3; NT-3 growth factor receptor isoform X1 [KO:K05101] [EC:2.7.10.1]
103670203  SH2B2; SH2B adapter protein 2 isoform X1 [KO:K07193]
103657816  SH2B1; SH2B adapter protein 1 isoform X1 [KO:K12459]
103661281  SH2B3; LOW QUALITY PROTEIN: SH2B adapter protein 3 [KO:K12459]
103665736  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
103671891  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
103665409  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
103669173  LOW QUALITY PROTEIN: GTPase HRas-like [KO:K02833]
103671035  HRAS; GTPase HRas isoform X3 [KO:K02833]
103665244  KRAS; GTPase KRas isoform X1 [KO:K07827]
103669422  NRAS; GTPase NRas [KO:K07828]
103669540  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
103669103  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
103679064  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
103681834  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103669286  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
103657827  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
103660807  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X1 [KO:K04373] [EC:2.7.11.1]
103668171  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X1 [KO:K04373] [EC:2.7.11.1]
103666515  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X1 [KO:K04373] [EC:2.7.11.1]
103671984  RPS6KA6; ribosomal protein S6 kinase alpha-6 [KO:K04373] [EC:2.7.11.1]
103673837  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
103676372  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
103676164  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
103679291  KIDINS220; kinase D-interacting substrate of 220 kDa isoform X1 [KO:K12460]
103656877  FRS2; fibroblast growth factor receptor substrate 2 [KO:K12461]
103669230  CRKL; crk-like protein [KO:K04438]
103670406  RAPGEF1; rap guanine nucleotide exchange factor 1 [KO:K06277]
103675043  RAP1A; ras-related protein Rap-1A isoform X1 [KO:K04353]
103659828  ras-related protein Rap-1b-like [KO:K07836]
103656863  RAP1B; ras-related protein Rap-1b [KO:K07836]
103665628  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
103679052  MAP2K5; dual specificity mitogen-activated protein kinase kinase 5 isoform X1 [KO:K04463] [EC:2.7.12.2]
103658546  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
103674115  MAPK12; mitogen-activated protein kinase 12 [KO:K04441] [EC:2.7.11.24]
103665451  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
103665538  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
103674004  MAPK11; mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
103657756  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
103668383  SHC1; SHC-transforming protein 1 isoform X2 [KO:K06279]
103681753  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
103663185  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
103676722  SHC4; SHC-transforming protein 4 [KO:K17449]
103658080  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
103675162  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103663617  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
103670766  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103678592  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
103666874  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103676125  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103666688  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103661038  AKT2; RAC-beta serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
103676878  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
103661015  NFKBIB; LOW QUALITY PROTEIN: NF-kappa-B inhibitor beta [KO:K02581]
103666055  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
103664144  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
103677947  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
103679584  RELA; transcription factor p65 [KO:K04735]
103675835  FOXO3; forkhead box protein O3 [KO:K09408]
103668115  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
103679423  BAD; bcl2-associated agonist of cell death [KO:K02158]
103678785  GSK3B; glycogen synthase kinase-3 beta isoform X2 [KO:K03083] [EC:2.7.11.26]
103668498  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
103662712  IRS1; insulin receptor substrate 1 [KO:K16172]
103669754  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
103662093  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
103674744  PRKCD; protein kinase C delta type isoform X1 [KO:K06068] [EC:2.7.11.13]
103670304  CALM1; calmodulin-1 isoform X1 [KO:K02183]
103682041  CALML6; calmodulin-like protein 6 [KO:K02183]
103676238  calmodulin [KO:K02183]
103676239  CALML3; calmodulin-like protein 3 [KO:K02183]
103671240  CALM2; calmodulin-2 [KO:K02183]
103679049  CALML4; calmodulin-like protein 4 isoform X3 [KO:K02183]
103657204  CALM3; calmodulin-3 [KO:K02183]
103661761  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X3 [KO:K04515] [EC:2.7.11.17]
103664598  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
103668027  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
103674683  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
103675811  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
103670413  ABL1; tyrosine-protein kinase ABL1 [KO:K06619] [EC:2.7.10.2]
103661289  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
103682087  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
103681828  MATK; megakaryocyte-associated tyrosine-protein kinase [KO:K08888] [EC:2.7.10.2]
103661017  NGFR; tumor necrosis factor receptor superfamily member 16 [KO:K02583]
103677783  ARHGDIB; rho GDP-dissociation inhibitor 2 isoform X1 [KO:K12462]
103665820  ARHGDIA; rho GDP-dissociation inhibitor 1 [KO:K12462]
103668667  ARHGDIG; rho GDP-dissociation inhibitor 3 [KO:K12462]
103674825  RHOA; transforming protein RhoA [KO:K04513]
103666578  CDC42; cell division control protein 42 homolog [KO:K04393]
103670095  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
103663891  MAP3K1; mitogen-activated protein kinase kinase kinase 1 [KO:K04416] [EC:2.7.11.25]
103663496  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X2 [KO:K04426] [EC:2.7.11.25]
103681888  MAP2K7; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 7 [KO:K04431] [EC:2.7.12.2]
103676947  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
103679990  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
103667893  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
103670861  JUN; transcription factor AP-1 [KO:K04448]
103660368  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
103657107  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
103678460  TP73; tumor protein p73 [KO:K10148]
103659308  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
103677232  ZNF274; neurotrophin receptor-interacting factor homolog isoform X1 [KO:K12458]
103676456  PRDM4; PR domain zinc finger protein 4 isoform X1 [KO:K12463] [EC:2.1.1.-]
103676302  MAGED1; melanoma-associated antigen D1 isoform X1 [KO:K12464]
103674859  BEX3; protein BEX3 isoform X1 [KO:K12465]
103667175  14-3-3 protein epsilon [KO:K06630]
103661470  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
103679690  IRAK1; interleukin-1 receptor-associated kinase 1 [KO:K04730] [EC:2.7.11.1]
103669562  IRAK2; interleukin-1 receptor-associated kinase-like 2 [KO:K04731] [EC:2.7.11.1]
103656963  IRAK3; interleukin-1 receptor-associated kinase 3 isoform X1 [KO:K04732] [EC:2.7.11.1]
103675405  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
103677059  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta [KO:K07209] [EC:2.7.11.10]
103674994  SORT1; sortilin isoform X1 [KO:K12388]
103671416  PSEN1; presenilin-1 isoform X1 [KO:K04505] [EC:3.4.23.-]
103667043  PSEN2; presenilin-2 isoform X1 [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
umr04010  MAPK signaling pathway
umr04120  Ubiquitin mediated proteolysis
umr04210  Apoptosis
umr04720  Long-term potentiation
umr04810  Regulation of actin cytoskeleton
KO pathway
ko04722   
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