BDNF signaling in neurodevelopment (Homo sapiens)

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Description

Brain-derived neurotrophic factor (BDNF) is a neurotrophin essential for neuron growth, differentiation, plasticity, and survival. BDNF binds tropomyosin-related kinase B (TrkB) and p75 neurotrophin receptor (p75NTR) with low affinity. Binding to TrkB activates the receptor through dimerization and autophosphorylation, which leads to phosphobinding sites for adaptor proteins FRS2, SCH1, and SH2B2. These adaptor proteins activate CREB1 through the RAS/ERK pathway. IRS1/2 activates the PI3K/AKT pathway, resulting in the activation of beta-catenin. TrkB can form a complex with p75NTR, resulting in the activation of kiddins220, activating the RAS/ERK pathway from a different route. Binding of pto-BNDF to the P75NTR Sortilin dimer resulted in the recruitment of adaptor proteins such as RAC1/CDC42, TRADD/FAD, activating MAPK8 and caspase 8, respectively. Additionally, pro-BDNF binding induces the synthesis of ceramides, resulting in the inhibition of RAS.

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Bibliography

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History

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CompareRevisionActionTimeUserComment
139162view06:05, 24 May 2025Qiushantaly RosinaAddtion of new nodes and reorganization of the pathway
138907view08:46, 7 May 2025Qiushantaly RosinaOntology Term : 'neuron' added !
138906view08:39, 7 May 2025Qiushantaly RosinaOntology Term : 'brain-derived neurotrophic factor signaling pathway' added !
138905view08:34, 7 May 2025Qiushantaly RosinaMade the pathway more compact and added the missing identifiers
138904view07:49, 7 May 2025Qiushantaly RosinaNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AKT1GeneProductENSG00000142208 (Ensembl) leads to survival
APAF1GeneProductENSG00000120868 (Ensembl)
ARHGAP35GeneProductENSG00000160007 (Ensembl)
ARHGDIAGeneProductENSG00000141522 (Ensembl)
BADGeneProductENSG00000002330 (Ensembl)
BAXGeneProductENSG00000087088 (Ensembl)
BCL2GeneProductENSG00000171791 (Ensembl) survival
BCL2L11GeneProductENSG00000153094 (Ensembl)
BDNFGeneProductENSG00000176697 (Ensembl)
BMP7GeneProductENSG00000101144 (Ensembl) generate astrocytes
CASP8GeneProductENSG00000064012 (Ensembl)
CASP9GeneProductENSG00000132906 (Ensembl)
CDC42GeneProductENSG00000070831 (Ensembl)
CFL1GeneProductENSG00000172757 (Ensembl)
CFL2GeneProductENSG00000165410 (Ensembl)
CHUKGeneProductENSG00000213341 (Ensembl)
CREB1GeneProductENSG00000118260 (Ensembl)
CRKGeneProductENSG00000167193 (Ensembl)
CTNNB1GeneProductENSG00000168036 (Ensembl) transcription factor
CYCSGeneProductENSG00000172115 (Ensembl)
Ca2+MetaboliteCHEBI:29108 (ChEBI)
CaMKIIGeneProductENSG00000004660.15 (Ensembl)
DAG MetaboliteCHEBI:18035 (ChEBI)
DIAPH1GeneProductENSG00000131504 (Ensembl) microtubule stability -> axon growth
DOCK7GeneProductENSG00000116641 (Ensembl)
EEF2GeneProductENSG00000167658 (Ensembl)
EEF2KGeneProductENSG00000103319 (Ensembl)
EIF4EBP1GeneProductENSG00000187840 (Ensembl)
EIF4EGeneProductENSG00000151247 (Ensembl)
FADDGeneProductENSG00000168040 (Ensembl)
FOXO3GeneProductENSG00000118689 (Ensembl)
FRS2GeneProductENSG00000166225 (Ensembl)
GAB1GeneProductENSG00000109458 (Ensembl)
GRB2GeneProductENSG00000177885 (Ensembl)
GSK3BGeneProductENSG00000082701 (Ensembl)
  • axonal growth
  • cell cycle regulation through downstream effects
HRASGeneProductENSG00000174775 (Ensembl)
IKB Complexcpx-3269 (ChEBI)
IKBKBGeneProductENSG00000104365 (Ensembl)
IKBKGGeneProductENSG00000269335 (Ensembl)
IP3MetaboliteCHEBI:16595 (ChEBI)
IQGAP3GeneProductENSG00000183856 (Ensembl) cytoskeletal rearrangement
IRS1GeneProductENSG00000169047 (Ensembl)
IRS2GeneProductENSG00000185950 (Ensembl)
JUNGeneProductENSG00000177606 (Ensembl)
KIDINS220GeneProductENSG00000134313 (Ensembl)
KRASGeneProductENSG00000133703 (Ensembl)
LEF1GeneProductENSG00000138795 (Ensembl)
LIMK1GeneProductENSG00000106683 (Ensembl)
LINGO1GeneProductENSG00000169783 (Ensembl)
MAP2K1GeneProductENSG00000169032 (Ensembl)
MAP2K2GeneProductENSG00000126934 (Ensembl)
MAP2K4GeneProductENSG00000065559 (Ensembl)
MAP2K5GeneProductENSG00000137764 (Ensembl)
MAP2K7GeneProductENSG00000076984 (Ensembl)
MAP3K1GeneProductENSG00000095015 (Ensembl)
MAP3K3GeneProductENSG00000198909 (Ensembl)
MAP3K5GeneProductENSG00000197442 (Ensembl)
MAPK11GeneProductENSG00000185386 (Ensembl)
MAPK1GeneProductENSG00000100030 (Ensembl)
MAPK3GeneProductENSG00000102882 (Ensembl)
MAPK7GeneProductENSG00000166484 (Ensembl)
MAPK8GeneProductENSG00000107643 (Ensembl)
MAPKAPK2GeneProductENSG00000162889 (Ensembl)
MKNK1GeneProductENSG00000079277 (Ensembl)
MTORGeneProductENSG00000198793 (Ensembl)
MYCGeneProductENSG00000136997 (Ensembl) cell cycle regulation
NFKBIAGeneProductENSG00000100906 (Ensembl)
  • survival
  • retrograde transport
NGFRGeneProductENSG00000064300 (Ensembl)
NPTX2GeneProductENSG00000106236 (Ensembl)
NRASGeneProductENSG00000213281 (Ensembl)
NTRK2GeneProductENSG00000148053 (Ensembl)
PAK1GeneProductENSG00000149269 (Ensembl)
  • cytoskeletal rearrangement
  • CDC42, RAC - actin polymerization
PARD3GeneProductENSG00000148498 (Ensembl) cytoskeletal rearrangement
PARD6AGeneProductENSG00000102981 (Ensembl)
PARD6BGeneProductENSG00000124171 (Ensembl)
PDPK1GeneProductENSG00000140992 (Ensembl)
PIK3CAGeneProductENSG00000121879 (Ensembl)
PIK3CBGeneProductENSG00000051382 (Ensembl)
PIK3CDGeneProductENSG00000171608 (Ensembl)
PIK3CGGeneProductENSG00000105851 (Ensembl)
PIP2MetaboliteCHEBI:18348 (ChEBI)
PIP3MetaboliteCHEBI:16618 (ChEBI)
PLCG1GeneProductENSG00000124181 (Ensembl)
PRKCAGeneProductENSG00000154229 (Ensembl)
PRKCBGeneProductENSG00000166501 (Ensembl)
PRKCDGeneProductENSG00000163932 (Ensembl)
PRKCEGeneProductENSG00000171132 (Ensembl)
PRKCGGeneProductENSG00000126583 (Ensembl)
PRKCHGeneProductENSG00000027075 (Ensembl)
PRKCIGeneProductENSG00000163558 (Ensembl)
PRKCZGeneProductENSG00000067606 (Ensembl)
PTPN11GeneProductENSG00000179295 (Ensembl)
Pro-BDNFGeneProductENSG00000176697 (Ensembl)
RAC1GeneProductENSG00000136238 (Ensembl)
  • morphological plasticity
  • tiam - cell morphology, adhesion, migration, and polarity
  • dock7 - microtubule stability
RAF1GeneProductENSG00000132155 (Ensembl)
RAP1BGeneProductENSG00000127314 (Ensembl)
RAPGEF1GeneProductENSG00000107263 (Ensembl)
RHOAGeneProductENSG00000067560 (Ensembl)
RND3GeneProductENSG00000115963 (Ensembl)
ROCK1GeneProductENSG00000067900 (Ensembl)
ROCK2GeneProductENSG00000134318 (Ensembl)
RPS6KB1GeneProductENSG00000108443 (Ensembl)
RPS6KB2GeneProductENSG00000175634 (Ensembl)
RTN4RGeneProductENSG00000040608 (Ensembl)
SH2B2GeneProductENSG00000160999 (Ensembl)
SHC1GeneProductENSG00000160691 (Ensembl)
SMPD1GeneProductENSG00000166311 (Ensembl)
SORT1GeneProductENSG00000134243 (Ensembl)
SOS1GeneProductENSG00000115904 (Ensembl)
STAT3GeneProductENSG00000168610 (Ensembl)
STMN1GeneProductENSG00000117632 (Ensembl) -RAC- microtubule stability
TCF7GeneProductENSG00000081059 (Ensembl)
TCF7L1GeneProductENSG00000152284 (Ensembl)
TCF7L2GeneProductENSG00000148737 (Ensembl)
TIAM1GeneProductENSG00000156299 (Ensembl)
TIAM2GeneProductENSG00000146426 (Ensembl)
TP53GeneProductENSG00000141510 (Ensembl)
TP73GeneProductENSG00000078900 (Ensembl)
TRADDGeneProductENSG00000102871 (Ensembl)
TRAF6GeneProductENSG00000175104 (Ensembl)
WASLGeneProductENSG00000106299 (Ensembl) cytoskeletal rearrangement
YWHABGeneProductENSG00000166913 (Ensembl)
YWHAEGeneProductENSG00000108953 (Ensembl)
YWHAGGeneProductENSG00000170027 (Ensembl)
YWHAHGeneProductENSG00000128245 (Ensembl)
YWHAQGeneProductENSG00000134308 (Ensembl)
YWHAZGeneProductENSG00000164924 (Ensembl)
ceramidesMetaboliteCHEBI:17761 (ChEBI)

Annotated Interactions

No annotated interactions

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