KEGG   PATHWAY: hmh04722
Entry
hmh04722                    Pathway                                
Name
Neurotrophin signaling pathway - Hylobates moloch (silvery gibbon)
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
hmh04722  Neurotrophin signaling pathway
hmh04722

Organism
Hylobates moloch (silvery gibbon) [GN:hmh]
Gene
116468350  NGF; beta-nerve growth factor [KO:K02582]
116476405  BDNF; brain-derived neurotrophic factor isoform X1 [KO:K04355]
116478219  NTF4; neurotrophin-4 [KO:K12457]
116472566  NTF3; neurotrophin-3 isoform X1 [KO:K04356]
116467918  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
116475199  NTRK2; BDNF/NT-3 growth factors receptor isoform X2 [KO:K04360] [EC:2.7.10.1]
116482214  NTRK3; NT-3 growth factor receptor isoform X3 [KO:K05101] [EC:2.7.10.1]
116810979  SH2B2; SH2B adapter protein 2 isoform X1 [KO:K07193]
116477920  SH2B3; SH2B adapter protein 3 isoform X3 [KO:K12459]
116470193  SH2B1; SH2B adapter protein 1 isoform X1 [KO:K12459]
116484153  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
116484062  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
116484470  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
116466571  HRAS; GTPase HRas isoform X3 [KO:K02833]
116472788  KRAS; GTPase KRas isoform X1 [KO:K07827]
116469568  NRAS; GTPase NRas [KO:K07828]
116466754  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
116814428  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
116482295  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116814342  dual specificity mitogen-activated protein kinase kinase 2-like [KO:K04369] [EC:2.7.12.2]
116483548  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
116459126  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116470222  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
116811564  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X2 [KO:K04373] [EC:2.7.11.1]
116811841  RPS6KA6; ribosomal protein S6 kinase alpha-6 isoform X2 [KO:K04373] [EC:2.7.11.1]
116813127  RPS6KA1; ribosomal protein S6 kinase alpha-1 isoform X1 [KO:K04373] [EC:2.7.11.1]
116473757  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X1 [KO:K04373] [EC:2.7.11.1]
116456094  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
116458613  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
116810327  LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-4-like [KO:K04374]
116468493  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
116480202  KIDINS220; kinase D-interacting substrate of 220 kDa isoform X3 [KO:K12460]
116478996  FRS2; fibroblast growth factor receptor substrate 2 [KO:K12461]
116458283  CRK; adapter molecule crk isoform X1 [KO:K04438]
116458915  CRKL; crk-like protein [KO:K04438]
116475789  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X1 [KO:K06277]
116469612  RAP1A; ras-related protein Rap-1A [KO:K04353]
116478979  RAP1B; ras-related protein Rap-1b [KO:K07836]
116458740  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
116482344  MAP2K5; dual specificity mitogen-activated protein kinase kinase 5 isoform X3 [KO:K04463] [EC:2.7.12.2]
116483083  MAPK7; mitogen-activated protein kinase 7 isoform X1 [KO:K04464] [EC:2.7.11.24]
116458518  MAPK12; mitogen-activated protein kinase 12 isoform X2 [KO:K04441] [EC:2.7.11.24]
116458519  MAPK11; mitogen-activated protein kinase 11 isoform X1 [KO:K04441] [EC:2.7.11.24]
116459642  MAPK14; mitogen-activated protein kinase 14 isoform X1 [KO:K04441] [EC:2.7.11.24]
116459649  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
116457332  MAPKAPK2; MAP kinase-activated protein kinase 2 isoform X2 [KO:K04443] [EC:2.7.11.1]
116469345  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
116464630  SHC-transforming protein 2-like [KO:K17447]
116475219  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
116481523  SHC4; SHC-transforming protein 4 [KO:K17449]
116464438  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
116478691  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
116462749  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
116473104  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
116462105  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116812889  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116481263  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
116457903  AKT3; RAC-gamma serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116485139  AKT1; RAC-alpha serine/threonine-protein kinase isoform X1 [KO:K04456] [EC:2.7.11.1]
116480683  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
116480724  NFKBIB; NF-kappa-B inhibitor beta isoform X1 [KO:K02581]
116484638  NFKBIA; NF-kappa-B inhibitor alpha [KO:K04734]
116460215  NFKBIE; LOW QUALITY PROTEIN: NF-kappa-B inhibitor epsilon [KO:K05872]
116483343  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
116469011  RELA; transcription factor p65 isoform X1 [KO:K04735]
116470667  FOXO3; forkhead box protein O3 isoform X1 [KO:K09408]
116472296  FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
116468949  BAD; bcl2-associated agonist of cell death [KO:K02158]
116466895  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
116810145  IRS1; insulin receptor substrate 1 [KO:K16172]
116461010  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
116470775  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
116473376  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
116467516  uncharacterized protein LOC116467516 [KO:K02183]
116485193  CALM1; calmodulin-1 isoform X2 [KO:K02183]
116478308  CALM3; calmodulin-3 [KO:K02183]
116482339  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
116813883  CALML6; calmodulin-like protein 6 [KO:K02183]
116483146  CALM2; calmodulin-2 isoform X1 [KO:K02183]
116466871  calmodulin-1-like [KO:K02183]
116474613  CALML5; calmodulin-like protein 5 [KO:K02183]
116474621  CALML3; calmodulin-like protein 3 [KO:K02183]
116459675  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
116471714  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
116812488  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
116463099  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X2 [KO:K04515] [EC:2.7.11.17]
116470946  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
116475772  ABL1; tyrosine-protein kinase ABL1 isoform X1 [KO:K06619] [EC:2.7.10.2]
116477894  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
116813270  LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
116466981  LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
116482876  MATK; megakaryocyte-associated tyrosine-protein kinase isoform X1 [KO:K08888] [EC:2.7.10.2]
116474666  NGFR; tumor necrosis factor receptor superfamily member 16 [KO:K02583]
116472726  ARHGDIB; rho GDP-dissociation inhibitor 2 [KO:K12462]
116465380  ARHGDIG; rho GDP-dissociation inhibitor 3 [KO:K12462]
116483656  ARHGDIA; rho GDP-dissociation inhibitor 1 [KO:K12462]
116469279  transforming protein RhoA-like [KO:K04513]
116473478  RHOA; transforming protein RhoA [KO:K04513]
116813051  CDC42; cell division control protein 42 homolog isoform X2 [KO:K04393]
116480287  ras-related C3 botulinum toxin substrate 1-like [KO:K04392]
116810870  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
116462248  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X1 [KO:K04416] [EC:2.7.11.25]
116472781  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform X1 [KO:K04426] [EC:2.7.11.25]
116478375  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
116460769  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
116471970  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
116463128  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
116457363  JUN; transcription factor Jun [KO:K04448]
116459052  TP53; cellular tumor antigen p53 [KO:K04451]
116478225  BAX; apoptosis regulator BAX isoform X3 [KO:K02159]
116812823  TP73; tumor protein p73 [KO:K10148]
116476347  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
116479287  ZNF274; neurotrophin receptor-interacting factor homolog isoform X1 [KO:K12458]
116477990  PRDM4; PR domain zinc finger protein 4 isoform X1 [KO:K12463] [EC:2.1.1.-]
116811704  MAGED1; melanoma-associated antigen D1 [KO:K12464]
116471412  protein BEX3 [KO:K12465]
116811900  BEX3; protein BEX3 isoform X1 [KO:K12465]
116458285  YWHAE; 14-3-3 protein epsilon [KO:K06630]
116813394  RIPK2; receptor-interacting serine/threonine-protein kinase 2 [KO:K08846] [EC:2.7.11.1]
116812171  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
116466544  IRAK2; interleukin-1 receptor-associated kinase-like 2 [KO:K04731] [EC:2.7.11.1]
116478968  IRAK3; interleukin-1 receptor-associated kinase 3 isoform X1 [KO:K04732] [EC:2.7.11.1]
116481090  IRAK4; interleukin-1 receptor-associated kinase 4 isoform X1 [KO:K04733] [EC:2.7.11.1]
116461632  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
116469660  SORT1; sortilin isoform X1 [KO:K12388]
116484654  PSEN1; presenilin-1 [KO:K04505] [EC:3.4.23.-]
116457564  PSEN2; presenilin-2 isoform X4 [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
hmh04010  MAPK signaling pathway
hmh04120  Ubiquitin mediated proteolysis
hmh04210  Apoptosis
hmh04720  Long-term potentiation
hmh04810  Regulation of actin cytoskeleton
KO pathway
ko04722   
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