KEGG   PATHWAY: mjv04722
Entry
mjv04722                    Pathway                                
Name
Neurotrophin signaling pathway - Manis javanica (Malayan pangolin)
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
mjv04722  Neurotrophin signaling pathway
mjv04722

Organism
Manis javanica (Malayan pangolin) [GN:mjv]
Gene
108386081  NGF; beta-nerve growth factor [KO:K02582]
108401589  BDNF; brain-derived neurotrophic factor isoform X1 [KO:K04355]
108400338  NTF4; neurotrophin-4 [KO:K12457]
108395105  NTF3; neurotrophin-3 isoform X1 [KO:K04356]
108383338  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
108400418  NTRK2; BDNF/NT-3 growth factors receptor isoform X1 [KO:K04360] [EC:2.7.10.1]
108402158  NTRK3; NT-3 growth factor receptor isoform X1 [KO:K05101] [EC:2.7.10.1]
108389845  SH2B2; SH2B adapter protein 2 isoform X5 [KO:K07193]
108385495  SH2B1; SH2B adapter protein 1 isoform X1 [KO:K12459]
108400539  SH2B3; SH2B adapter protein 3 isoform X1 [KO:K12459]
108400653  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
108391894  SOS2; son of sevenless homolog 2 [KO:K03099]
108385648  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
108408627  HRAS; GTPase HRas isoform X1 [KO:K02833]
118967667  GTPase HRas-like isoform X1 [KO:K02833]
108395842  KRAS; GTPase KRas isoform X1 [KO:K07827]
108398047  NRAS; GTPase NRas [KO:K07828]
108394341  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
108387830  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
108394305  LOW QUALITY PROTEIN: serine/threonine-protein kinase B-raf-like [KO:K04365] [EC:2.7.11.1]
108392139  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
108385046  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
108398454  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
108400663  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
108396401  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X2 [KO:K04373] [EC:2.7.11.1]
108397840  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X1 [KO:K04373] [EC:2.7.11.1]
108401853  RPS6KA6; ribosomal protein S6 kinase alpha-6 isoform X1 [KO:K04373] [EC:2.7.11.1]
108404175  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X1 [KO:K04373] [EC:2.7.11.1]
108401059  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
108397369  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
108385222  BCL2; apoptosis regulator Bcl-2 isoform X1 [KO:K02161]
108384273  KIDINS220; kinase D-interacting substrate of 220 kDa isoform X2 [KO:K12460]
108405521  FRS2; fibroblast growth factor receptor substrate 2 [KO:K12461]
108408988  CRKL; crk-like protein [KO:K04438]
108394533  CRK; adapter molecule crk isoform X1 [KO:K04438]
108406801  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X18 [KO:K06277]
108395546  RAP1A; ras-related protein Rap-1A [KO:K04353]
108407356  RAP1B; ras-related protein Rap-1b isoform X1 [KO:K07836]
108392641  LOW QUALITY PROTEIN: ras-related protein Rap-1b-like [KO:K07836]
108401834  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
108409326  MAP2K5; dual specificity mitogen-activated protein kinase kinase 5 [KO:K04463] [EC:2.7.12.2]
108409115  MAPK7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:2.7.11.24]
108395598  MAPK12; mitogen-activated protein kinase 12 isoform X9 [KO:K04441] [EC:2.7.11.24]
108394635  MAPK13; mitogen-activated protein kinase 13 isoform X1 [KO:K04441] [EC:2.7.11.24]
108394636  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
108403019  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
108407280  SHC-transforming protein 1 isoform X1 [KO:K06279]
118972101  SHC-transforming protein 1-like isoform X1 [KO:K06279]
108391745  SHC2; SHC-transforming protein 2 isoform X2 [KO:K17447]
108394387  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
108402352  SHC4; SHC-transforming protein 4 [KO:K17449]
108409341  GAB1; GRB2-associated-binding protein 1 isoform X6 [KO:K09593]
108383561  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
108390475  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
108395975  phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
108406544  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
108390365  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108400388  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
108397433  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
108390484  AKT2; RAC-beta serine/threonine-protein kinase isoform X3 [KO:K04456] [EC:2.7.11.1]
108393746  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
108395444  NFKBIB; NF-kappa-B inhibitor beta [KO:K02581]
108402523  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
108407145  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
108391706  NFKB1; nuclear factor NF-kappa-B p105 subunit [KO:K02580]
108397005  RELA; transcription factor p65 isoform X1 [KO:K04735]
108390100  FOXO3; forkhead box protein O3 [KO:K09408]
108401438  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
108407571  BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
108389003  GSK3B; glycogen synthase kinase-3 beta isoform X5 [KO:K03083] [EC:2.7.11.26]
108399811  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X3 [KO:K06276] [EC:2.7.11.1]
108397189  IRS1; insulin receptor substrate 1 [KO:K16172]
108407248  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
108400464  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
108408298  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
108406654  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
108386142  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
108383704  calmodulin-A-like [KO:K02183]
108406136  CALM3; calmodulin-3 [KO:K02183]
108391461  CALM2; calmodulin-2 [KO:K02183]
108389026  CALM1; calmodulin-1 [KO:K02183]
108385398  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
108394027  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
108398760  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
108400883  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
108390709  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
108408195  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
108405695  tyrosine-protein phosphatase non-receptor type 11-like isoform X1 [KO:K07293] [EC:3.1.3.48]
108384781  MATK; LOW QUALITY PROTEIN: megakaryocyte-associated tyrosine-protein kinase [KO:K08888] [EC:2.7.10.2]
108391063  NGFR; tumor necrosis factor receptor superfamily member 16 isoform X1 [KO:K02583]
108408104  ARHGDIG; rho GDP-dissociation inhibitor 3 [KO:K12462]
108395236  ARHGDIA; rho GDP-dissociation inhibitor 1 [KO:K12462]
108403131  ARHGDIB; rho GDP-dissociation inhibitor 2 isoform X1 [KO:K12462]
108383250  transforming protein RhoA [KO:K04513]
108391531  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
108407595  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
108384016  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X2 [KO:K04416] [EC:2.7.11.25]
108401094  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
108409616  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
108396943  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
108384893  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
108385635  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
108386817  JUN; transcription factor AP-1 [KO:K04448]
108404266  TP53; cellular tumor antigen p53 [KO:K04451]
118974052  cellular tumor antigen p53 [KO:K04451]
108400315  BAX; apoptosis regulator BAX isoform X1 [KO:K02159]
118969429  apoptosis regulator BAX [KO:K02159]
108386315  TP73; tumor protein p73 isoform X1 [KO:K10148]
108390300  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
108387098  ZNF274; neurotrophin receptor-interacting factor homolog [KO:K12458]
108399358  PRDM4; PR domain zinc finger protein 4 isoform X1 [KO:K12463] [EC:2.1.1.-]
108402736  MAGED1; melanoma-associated antigen D1 [KO:K12464]
108397332  BEX3; protein BEX3 [KO:K12465]
108394547  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
108395321  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
108409511  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
108408138  interleukin-1 receptor-associated kinase-like 2 isoform X1 [KO:K04731] [EC:2.7.11.1]
108405730  IRAK3; interleukin-1 receptor-associated kinase 3 [KO:K04732] [EC:2.7.11.1]
108396677  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
108399795  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
108400474  SORT1; sortilin [KO:K12388]
108395378  PSEN1; presenilin-1 [KO:K04505] [EC:3.4.23.-]
108396215  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
mjv04010  MAPK signaling pathway
mjv04120  Ubiquitin mediated proteolysis
mjv04210  Apoptosis
mjv04720  Long-term potentiation
mjv04810  Regulation of actin cytoskeleton
KO pathway
ko04722   
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