KEGG   PATHWAY: shr04722
Entry
shr04722                    Pathway                                
Name
Neurotrophin signaling pathway - Sarcophilus harrisii (Tasmanian devil)
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
shr04722  Neurotrophin signaling pathway
shr04722

Organism
Sarcophilus harrisii (Tasmanian devil) [GN:shr]
Gene
100930279  NGF; beta-nerve growth factor [KO:K02582]
100934810  BDNF; brain-derived neurotrophic factor isoform X2 [KO:K04355]
100918745  NTF3; neurotrophin-3 isoform X1 [KO:K04356]
100916388  NTRK1; high affinity nerve growth factor receptor [KO:K03176] [EC:2.7.10.1]
100927322  NTRK2; BDNF/NT-3 growth factors receptor isoform X1 [KO:K04360] [EC:2.7.10.1]
100926082  NTRK3; NT-3 growth factor receptor isoform X2 [KO:K05101] [EC:2.7.10.1]
100929846  SH2B2; SH2B adapter protein 2 isoform X1 [KO:K07193]
100919741  SH2B3; SH2B adapter protein 3 [KO:K12459]
100913226  SH2B1; SH2B adapter protein 1 isoform X3 [KO:K12459]
100928380  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100931009  SOS1; son of sevenless homolog 1 isoform X2 [KO:K03099]
100932999  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
100929168  ras-like protein [KO:K02833]
116419913  HRAS; GTPase HRas [KO:K02833]
100915526  KRAS; GTPase KRas isoform X1 [KO:K07827]
100927252  ras-related protein Rab-26-like [KO:K07827]
100929426  ras protein let-60-like [KO:K07827]
100928986  NRAS; GTPase NRas [KO:K07828]
100935202  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
100934801  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
100921899  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
100917396  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
100934330  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100913231  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
100923157  LOW QUALITY PROTEIN: ribosomal protein S6 kinase alpha-1 [KO:K04373] [EC:2.7.11.1]
100928498  RPS6KA6; ribosomal protein S6 kinase alpha-6 [KO:K04373] [EC:2.7.11.1]
100931854  RPS6KA2; ribosomal protein S6 kinase alpha-2 isoform X2 [KO:K04373] [EC:2.7.11.1]
100931566  RPS6KA3; ribosomal protein S6 kinase alpha-3 isoform X4 [KO:K04373] [EC:2.7.11.1]
116422810  RPS6KA1; LOW QUALITY PROTEIN: ribosomal protein S6 kinase alpha-1 [KO:K04373] [EC:2.7.11.1]
100931885  RPS6KA5; ribosomal protein S6 kinase alpha-5 isoform X1 [KO:K04445] [EC:2.7.11.1]
100913697  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100934666  BCL2; apoptosis regulator Bcl-2 [KO:K02161]
100929446  KIDINS220; kinase D-interacting substrate of 220 kDa isoform X4 [KO:K12460]
100919610  FRS2; fibroblast growth factor receptor substrate 2 [KO:K12461]
100923581  CRKL; crk-like protein [KO:K04438]
116423462  CRK; adapter molecule crk isoform X1 [KO:K04438]
100914252  RAPGEF1; rap guanine nucleotide exchange factor 1 isoform X5 [KO:K06277]
100935403  RAP1A; ras-related protein Rap-1A isoform X2 [KO:K04353]
100920135  RAP1B; ras-related protein Rap-1b [KO:K07836]
100933837  MAP3K3; mitogen-activated protein kinase kinase kinase 3 isoform X1 [KO:K04421] [EC:2.7.11.25]
100924259  MAP2K5; dual specificity mitogen-activated protein kinase kinase 5 isoform X1 [KO:K04463] [EC:2.7.12.2]
100917749  MAPK7; mitogen-activated protein kinase 7 [KO:K04464] [EC:2.7.11.24]
100928729  MAPK12; mitogen-activated protein kinase 12 isoform X1 [KO:K04441] [EC:2.7.11.24]
100928990  MAPK11; LOW QUALITY PROTEIN: mitogen-activated protein kinase 11 [KO:K04441] [EC:2.7.11.24]
100925013  MAPK14; mitogen-activated protein kinase 14 isoform X2 [KO:K04441] [EC:2.7.11.24]
100925447  MAPK13; mitogen-activated protein kinase 13 [KO:K04441] [EC:2.7.11.24]
100917693  MAPKAPK2; MAP kinase-activated protein kinase 2 [KO:K04443] [EC:2.7.11.1]
100926921  SHC1; SHC-transforming protein 1 isoform X4 [KO:K06279]
100917745  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
100914800  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
100927458  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
100925463  GAB1; GRB2-associated-binding protein 1 isoform X1 [KO:K09593]
100926892  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100924976  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
100935230  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
100929811  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
100932099  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
105749979  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
100917987  AKT1; RAC-alpha serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100913262  AKT3; RAC-gamma serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100925440  AKT2; RAC-beta serine/threonine-protein kinase [KO:K04456] [EC:2.7.11.1]
100919027  NFKBIA; LOW QUALITY PROTEIN: NF-kappa-B inhibitor alpha [KO:K04734]
100914731  NFKBIE; NF-kappa-B inhibitor epsilon [KO:K05872]
100917619  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
100932473  RELA; transcription factor p65 [KO:K04735]
100917083  FOXO3; forkhead box protein O3 [KO:K09408]
100919776  FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
100923199  BAD; bcl2-associated agonist of cell death isoform X1 [KO:K02158]
100920192  GSK3B; glycogen synthase kinase-3 beta isoform X1 [KO:K03083] [EC:2.7.11.26]
100917568  PDPK1; 3-phosphoinositide-dependent protein kinase 1 isoform X1 [KO:K06276] [EC:2.7.11.1]
100918116  IRS1; insulin receptor substrate 1 [KO:K16172]
100923119  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
100919206  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X2 [KO:K05859] [EC:3.1.4.11]
100925245  PRKCD; protein kinase C delta type [KO:K06068] [EC:2.7.11.13]
100929017  CALM1; calmodulin-1 isoform X2 [KO:K02183]
100920429  CALM2; calmodulin-2 [KO:K02183]
105750699  calmodulin-A [KO:K02183]
100935134  CALM3; calmodulin-3 isoform X1 [KO:K02183]
100925046  CALML4; calmodulin-like protein 4 [KO:K02183]
116419081  calmodulin [KO:K02183]
116423459  calmodulin-like [KO:K02183]
116423460  calmodulin-like [KO:K02183]
100934917  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
100916233  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
100913975  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
100918427  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
100920792  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
100930047  ABL1; tyrosine-protein kinase ABL1 isoform X2 [KO:K06619] [EC:2.7.10.2]
100930062  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
100915682  LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
100916088  MATK; megakaryocyte-associated tyrosine-protein kinase isoform X1 [KO:K08888] [EC:2.7.10.2]
100931911  death domain-containing membrane protein NRADD [KO:K02583]
100927086  NGFR; tumor necrosis factor receptor superfamily member 16 [KO:K02583]
100922282  ARHGDIG; rho GDP-dissociation inhibitor 3 isoform X2 [KO:K12462]
100925804  ARHGDIB; rho GDP-dissociation inhibitor 2 isoform X2 [KO:K12462]
100920995  ARHGDIA; rho GDP-dissociation inhibitor 1 [KO:K12462]
100921931  RHOA; transforming protein RhoA [KO:K04513]
100918370  CDC42; cell division control protein 42 homolog isoform X1 [KO:K04393]
100919657  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
100913571  MAP3K1; mitogen-activated protein kinase kinase kinase 1 isoform X2 [KO:K04416] [EC:2.7.11.25]
100917439  MAP3K5; mitogen-activated protein kinase kinase kinase 5 [KO:K04426] [EC:2.7.11.25]
100926110  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform X1 [KO:K04431] [EC:2.7.12.2]
100930815  MAPK8; mitogen-activated protein kinase 8 isoform X1 [KO:K04440] [EC:2.7.11.24]
100928480  MAPK10; mitogen-activated protein kinase 10 isoform X1 [KO:K04440] [EC:2.7.11.24]
100924267  MAPK9; mitogen-activated protein kinase 9 isoform X1 [KO:K04440] [EC:2.7.11.24]
116423739  JUN; transcription factor AP-1 [KO:K04448]
100922473  TP53; cellular tumor antigen p53 isoform X1 [KO:K04451]
100918460  TP73; tumor protein p73 [KO:K10148]
100922331  TRAF6; TNF receptor-associated factor 6 [KO:K03175] [EC:2.3.2.27]
100927699  PRDM4; PR domain zinc finger protein 4 [KO:K12463] [EC:2.1.1.-]
100923627  LOW QUALITY PROTEIN: PR domain zinc finger protein 4 [KO:K12463] [EC:2.1.1.-]
100922737  YWHAE; 14-3-3 protein epsilon isoform X1 [KO:K06630]
100920956  RIPK2; receptor-interacting serine/threonine-protein kinase 2 isoform X1 [KO:K08846] [EC:2.7.11.1]
100923900  IRAK1; interleukin-1 receptor-associated kinase 1 isoform X1 [KO:K04730] [EC:2.7.11.1]
100932591  IRAK2; interleukin-1 receptor-associated kinase-like 2 isoform X1 [KO:K04731] [EC:2.7.11.1]
100914481  IRAK3; interleukin-1 receptor-associated kinase 3 isoform X1 [KO:K04732] [EC:2.7.11.1]
100934112  IRAK4; interleukin-1 receptor-associated kinase 4 [KO:K04733] [EC:2.7.11.1]
100928932  IKBKB; inhibitor of nuclear factor kappa-B kinase subunit beta isoform X1 [KO:K07209] [EC:2.7.11.10]
100921440  SORT1; sortilin isoform X1 [KO:K12388]
100914418  PSEN1; presenilin-1 [KO:K04505] [EC:3.4.23.-]
100928719  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
shr04010  MAPK signaling pathway
shr04120  Ubiquitin mediated proteolysis
shr04210  Apoptosis
shr04720  Long-term potentiation
shr04810  Regulation of actin cytoskeleton
KO pathway
ko04722   
LinkDB

DBGET integrated database retrieval system