BDNF signaling pathway (WP3141)

Bos taurus

Brain-derived neurotrophic factor (BDNF) is a neurotrophin essential for growth, differentiation, plasticity, and survival of neurons. BDNF is also required for processes such as energy metabolism, behavior, mental health, learning, memory, stress, pain and apoptosis. BDNF is implicated in various neuronal disorders such as Alzheimer's disease, Huntington's disease, depression, and bipolar disorder. BDNF binds to tyrosine kinase receptor known as tropomyosin-related kinase B (TrkB). It also binds with low affinity to p75 neurotrophin receptor (p75NTR). BDNF and its receptors are expressed throughout the central and peripheral nervous system. BDNF signaling is elicited when it dimerizes and binds to TrkB, resulting in the receptor dimerization and autophosphorylation. The activation of the receptor results in its interaction with molecules such as Shp2, Shc and PLC-gamma. These molecules further interact and modify their downstream targets leading to various neuronal processes. BDNF activates the signaling cascades such as PLC/PKC, PI3K/Akt, Ras/Erk, AMPK/ACC and NFκB pathways. BDNF through PLC/PKC pathway leads to release of intracellular calcium and regulation of synaptic plasticity. It also maintains synaptic plasticity through cAMP/PKA signaling. Activation of PI3K/Akt pathway through BDNF/TrkB interaction inhibits cell apoptosis by decreasing the expression of BIM. However, BDNF/p75NTR interaction activates JNK through TRAF6, which leads to apoptosis. Activation of JNK3 also leads to proteolytic cleavage of the p75NTR by TACE. PI3K/Akt also leads to activation of mTOR pathway and subsequently protein synthesis. Ras/Erk signaling is involved in cell proliferation, differentiation and protection of neurons. BDNF also leads to neuronal survival through Erk5/Mef pathway. Phosphorylation of synapsin by Erk1/2 leads to neurotransmitter release. BDNF signaling leads to nitric oxide production through NFκB pathway. BDNF induces neurite outgrowth through activation of JAK/STAT, Rac, and Cdc42 pathways. BDNF enhances oxidation of fat through AMPK mediated inhibition of ACC. It also plays role in microtubule assembly through inhibition of GSK3-beta. It leads to oxidative neuronal necrosis through activation of NCF molecules. BDNF also regulates the surface expression of AMPA and NMDA receptors. BDNF also regulates the expression of genes leading to processes such as differentiation of dendrites and calcification of cementoblast-like cells.

Authors

Martina Summer-Kutmon

Activity

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Organisms

Bos taurus

Communities

Annotations

Pathway Ontology

brain-derived neurotrophic factor signaling pathway

Participants

Label Type Compact URI Comment
IP3 Metabolite hmdb:HMDB0001143
PIP2 Metabolite chebi:18348
PIP3 Metabolite chebi:16618
cAMP Metabolite chebi:17489
IKBKB GeneProduct ensembl:ENSBTAG00000007599 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3551
IKBKG GeneProduct ensembl:ENSBTAG00000006268 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8517
CHUK GeneProduct ensembl:ENSBTAG00000007591 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1147
VAV3 Protein ensembl:ENSBTAG00000031575 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10451
MAPK9 Protein ensembl:ENSBTAG00000004709 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5601
CDK5R1 Protein ensembl:ENSBTAG00000004475 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8851
SHC2 Protein ensembl:ENSBTAG00000016072 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:25759
MAPK8 Protein ensembl:ENSBTAG00000007876 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5599
MAPK3 Protein ensembl:ENSBTAG00000016156 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
NCK1 Protein ensembl:ENSBTAG00000018427 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4690
NCK2 Protein ensembl:ENSBTAG00000015205 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8440
SHC1 Protein ensembl:ENSBTAG00000019838 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6464
PLCG1 Protein ensembl:ENSBTAG00000017584 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5335
PTPN11 Protein ensembl:ENSBTAG00000002048 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5781
CDH2 Protein ensembl:ENSBTAG00000021190 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1000
TRAF6 Protein ensembl:ENSBTAG00000036009 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7189
CTNNB1 Protein ensembl:ENSBTAG00000016420 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1499
SQSTM1 Protein ensembl:ENSBTAG00000015591 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8878
FYN Protein ensembl:ENSBTAG00000011851 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2534
SHC3 Protein ensembl:ENSBTAG00000011375 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:53358
NGFR Protein ensembl:ENSBTAG00000020979 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4804
NCAM1 Protein ensembl:ENSBTAG00000005710 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4684
TIAM1 Protein ensembl:ENSBTAG00000017839 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7074
LINGO1 Protein ensembl:ENSBTAG00000023147 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:84894
RANBP9 Protein ensembl:ENSBTAG00000021556 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10048
DOK5 Protein ensembl:ENSBTAG00000047975 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:55816
SHC4 Protein ensembl:ENSBTAG00000022583 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:399694
GRB2 Protein ensembl:ENSBTAG00000004736 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2885
SIRPB1 Protein ensembl:ENSBTAG00000039520 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:140885
KCNA3 Protein ensembl:ENSBTAG00000047879 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3738
FRS2 Protein ensembl:ENSBTAG00000019155 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10818
FRS3 Protein ensembl:ENSBTAG00000009861 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10817
DOCK3 Protein ensembl:ENSBTAG00000001874 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1795
NTRK1 Protein ensembl:ENSBTAG00000003060 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4914
RAC1 Protein ensembl:ENSBTAG00000009233 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5879
CDKL5 Protein ensembl:ENSBTAG00000007428 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6792
SORT1 Protein ensembl:ENSBTAG00000008849 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6272
NGF Protein ensembl:ENSBTAG00000007446 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4803
BDNF Protein ensembl:ENSBTAG00000008134 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:627
GRIA2 Protein ensembl:ENSBTAG00000004775 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2891
CREB1 Protein ensembl:ENSBTAG00000005474 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1385
NSF Protein ensembl:ENSBTAG00000008442 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4905
GNB2L1 Protein ensembl:ENSBTAG00000019648 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10399
GABRB3 Protein ensembl:ENSBTAG00000013422 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2562
PPP2CA Protein ensembl:ENSBTAG00000000469 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5515
CRTC1 Protein ensembl:ENSBTAG00000010379 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:23373
KSR1 Protein ensembl:ENSBTAG00000006601 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8844
MAP2K2 Protein ensembl:ENSBTAG00000024450 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5605
MAPK1 Protein ensembl:ENSBTAG00000010312 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
MAP2K1 Protein ensembl:ENSBTAG00000033983 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5604
SH2B2 Protein ensembl:ENSBTAG00000009691 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10603
FOXO3 Protein ensembl:ENSBTAG00000011234 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2309
MTOR Protein ensembl:ENSBTAG00000015325 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2475
KIDINS220 Protein ensembl:ENSBTAG00000007963 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:57498
RPS6KB1 Protein ensembl:ENSBTAG00000016851 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6198
EIF4EBP1 Protein ensembl:ENSBTAG00000027654 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1978
AKT1 Protein ensembl:ENSBTAG00000017636 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
BAD Protein ensembl:ENSBTAG00000012511 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:572
SH2B1 Protein ensembl:ENSBTAG00000019219 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:25970
GSK3B Protein ensembl:ENSBTAG00000048057 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2932
GRIN1 Protein ensembl:ENSBTAG00000047202 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2902
IRS2 Protein ensembl:ENSBTAG00000012019 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8660
MAPK7 Protein ensembl:ENSBTAG00000001014 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5598
IRS1 Protein ensembl:ENSBTAG00000021308 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3667
TSC2 Protein ensembl:ENSBTAG00000020617 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7249
GRIA1 Protein ensembl:ENSBTAG00000005800 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2890
CAMK4 Protein ensembl:ENSBTAG00000035662 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:814
CAMK2A Protein ensembl:ENSBTAG00000020087 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:815
EEF2 Protein ensembl:ENSBTAG00000004258 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1938
ACACB Protein ensembl:ENSBTAG00000022058 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:32
PRKAA2 Protein ensembl:ENSBTAG00000018747 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5563
MAPT Protein ensembl:ENSBTAG00000017512 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4137
ELK1 Protein ensembl:ENSBTAG00000015817 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2002
IGF2BP1 Protein ensembl:ENSBTAG00000011736 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10642
PTK2B Protein ensembl:ENSBTAG00000005958 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2185
RAF1 Protein ensembl:ENSBTAG00000045748 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5894
VAV2 Protein ensembl:ENSBTAG00000004511 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7410
CDK5 Protein ensembl:ENSBTAG00000007766 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1020
NFATC4 Protein ensembl:ENSBTAG00000006366 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4776
NCF2 Protein ensembl:ENSBTAG00000008004 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4688
NCF1 Protein ensembl:ENSBTAG00000003305 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:653361
STAT5B Protein ensembl:ENSBTAG00000010125 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6777
CDC42 Protein ensembl:ENSBTAG00000001700 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:998
CNR1 Protein ensembl:ENSBTAG00000046006 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1268
NTRK3 Protein ensembl:ENSBTAG00000047543 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4916
PIK3R1 Protein ensembl:ENSBTAG00000010989 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5295
NTF3 Protein ensembl:ENSBTAG00000010223 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4908
PDPK1 Protein ensembl:ENSBTAG00000034436 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5170
MAP3K1 Protein ensembl:ENSBTAG00000013790 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4214
ADAM17 Protein ensembl:ENSBTAG00000001141 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6868
MAPK10 Protein ensembl:ENSBTAG00000020048 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5602
HRAS Protein ensembl:ENSBTAG00000046644 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3265
RPS6 Protein ensembl:ENSBTAG00000014449 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6194
EIF4E Protein ensembl:ENSBTAG00000009522 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1977
SRC Protein ensembl:ENSBTAG00000008938 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6714
STAT5A Protein ensembl:ENSBTAG00000009496 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6776
NFKB1 Protein ensembl:ENSBTAG00000020270 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4790
RELA Protein ensembl:ENSBTAG00000013895 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5970
BIKBA Protein ensembl:ENSBTAG00000016683 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4792
JUN Protein ensembl:ENSBTAG00000004037 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3725
CASP3 Protein ensembl:ENSBTAG00000015874 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:836
RPS6KA3 Protein ensembl:ENSBTAG00000017639 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6197
YBX1 Protein ensembl:ENSBTAG00000017368 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4904
RPS6KA1 Protein ensembl:ENSBTAG00000014447 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6195
RPS6KA5 Protein ensembl:ENSBTAG00000010906 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:9252
CAMK1 Protein ensembl:ENSBTAG00000007780 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8536
MAPK14 Protein ensembl:ENSBTAG00000020783 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1432
RASGRF1 Protein ensembl:ENSBTAG00000019940 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5923
DPYSL2 Protein ensembl:ENSBTAG00000018373 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1808
APC Protein ensembl:ENSBTAG00000018852 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:324
PTPRF Protein ensembl:ENSBTAG00000000253 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5792
DLG1 Protein ensembl:ENSBTAG00000020378 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1739
GRIP1 Protein ensembl:ENSBTAG00000033726 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:23426
GRIA3 Protein ensembl:ENSBTAG00000011833 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2892
RHOG Protein ensembl:ENSBTAG00000000347 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:391
KCNN2 Protein ensembl:ENSBTAG00000011076 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3781
CFL1 Protein ensembl:ENSBTAG00000021455 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1072
PRKAA1 Protein ensembl:ENSBTAG00000000013 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5562
MAP2K5 Protein ensembl:ENSBTAG00000000218 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5607
MAP3K2 Protein ensembl:ENSBTAG00000004216 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:10746
MEF2C Protein ensembl:ENSBTAG00000020701 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4208
MEF2A Protein ensembl:ENSBTAG00000010649 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4205
RAP1A Protein ensembl:ENSBTAG00000014710 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5906
JAK2 Protein ensembl:ENSBTAG00000012047 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3717
STAT1 Protein ensembl:ENSBTAG00000007867 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6772
STAT3 Protein ensembl:ENSBTAG00000021523 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6774
PRKCD Protein ensembl:ENSBTAG00000008719 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5580
NTRK2 Protein ensembl:ENSBTAG00000010647 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4915
CSNK2A1 Protein ensembl:ENSBTAG00000012341 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1457
RAB3A Protein ensembl:ENSBTAG00000010635 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5864
EIF2S1 Protein ensembl:ENSBTAG00000016311 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1965
EIF2S2 Protein ensembl:ENSBTAG00000005969 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8894
SYN1 Protein ensembl:ENSBTAG00000005042 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6853

References