Brain-derived neurotrophic factor (BDNF) signaling pathway (Homo sapiens)

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VAV3MAPK9PCDK5R1SHC2MAPK8PMAPK3Y204T202ط®آ³-secretasecomplexCa2+ELMOIKKEndocytosis-dependentmembraneboundOxidativeneuronalnecrosisBrain-derived neurotrophic factor signaling pathwayDegradationSelectivepostsynapticdevelopmentNeuriteoutgrowthReduction inphosphorylationLamellipodia formationand increasedneurite outgrowthSynaptic plasticityDissociationProteinsynthesisBCL2L11IkkGIKK1IKK2CYFIP1NCK1NCK2SHC1PPLCG1Y783PTPN11PCDH2TRAF6CTNNB1Y654SQSTM1FYNY420SHC3PNGFRNCAM1Y734TIAM1Y829LINGO1RANBP9DOK5PSHC4PGRB2SIRPAPKCNA3PFRS2PGRIN2BPFRS3PDOCK3PNTRK1PRAC1CDKL5PSORT1NGFBDNFGRIA2CREB1S133NSFGNB2L1GABRB3S433S432PPP2CACRTC1KSR1MAP2K2PMAPK1Y187T185MAP2K1PSH2B2PFOXO3S253T32MTORS2448KIDINS220PRPS6KB1T412S447T444EIF4EBP1T37T46AKT1T308S473BADS99S75SH2BPGSK3BS9GRIN1PIRS2PMAPK7Y221T219IRS1PTSC2T1462GRIA1PCAMK4PCAMK2PEEF2ACACBS78PRKAA2T172MAPTS195S202S198ELK1PIGF2BP1Y396PTK2BY402RAF1S338VAV2Y172CDK5Y15NFATC4NCF2NCF1NFATC4CYNUCYNUSTAT5BCDC42CNR1NTRK3PIK3R1NTF3BDNFPDPK1S241MAP3K1ADAM17MAPK10PHRASGTPRPS6S240S244S235S236EIF4EPPIK3R2IP3SRCFOXO3PIP2DAGSTAT5ANFKB1RELAS529NFKB1RELAS529NFKBIAS36S32JUNPCASP3ProteinReceptorProteinProteinmRNASmall moleculeLigandInduced activationEnzyme complexInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through multiple reactionsTranslocation UbiquitinationPTM stateProtein-protein interactionDephosphorylationLEGENDPhosphorylationNucleusCytoplasmPlasma membraneCYPMNUProteolytic cleavageMoleculeCalcificationNeuronal growth,differentiation,and protectionInhibition ofapoptosisNitric oxideproductionApoptosisInhibition ofapoptosisRPS6KA3S227S386YBX1S102RPS6KA1S380S221RPS6KA5S376CAMK1T177MAPK14T180Y182RASGRF1DPYSL2T514APCPTPRFDLG1GRIP1GRIA3RHOGPAKKCNN2PCFL1PBDNFBDNFPIP2PIP3PIK3CACalmodulinSOSCAMKKCalcineurinPRKAA1T196EnhancedfatoxidationReduction in FOXO3 shuttleto nucleus anddecrease in BIMMAP2K5MAP3K2MEF2CMEF2ACerebellargranuleneuronalsurvivalCYNURAP1AMAPK7T219Y221CYNURegulation of surface expression of AMPA receptorsPKCRegulation ofsynaptic plasticitySTAT5BSTAT5AGrowthconemotilityCYNURegulation of Pre-synapticplasticity CYNUCYNUHuman airwaysmooth muscle cellproliferationRelease of RNG105from RNA granulesJAK2PSTAT1STAT3PPMajor pelvicganglia neuriteoutgrowthCEBPBFOSEGR1EGR2Cortical dendrite differentiationMARCKSPPRKCDY311CDK5dependentregulation of CDC42activityRadial migrationof corticalneuronsNTRK2Y722S495NTRK2K811Y723In secretorygranulesROSGSK3BS9MicrotubuleassemblyCSNK2A1RAB3AGTPcAMPPKASPP1ALPLBMP2EIF2S1EIF2S2MAPK3T202Y204MAPK1T185Y187SYN1PNeurotransmitterreleasemembraneboundBDNFBDNFBDNFAutocrinesignalingExtracellularECRPS6KA5S376ECCYDendritic developmentAxonal growthand branchingp75 NTR


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.

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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116399view00:01, 7 May 2021EweitzModified title
106345view21:34, 21 August 2019KhanspersModified description
106165view12:06, 16 August 2019MaintBotHMDB identifier normalization
105546view06:09, 9 August 2019KhanspersModified description
94178view13:37, 25 August 2017Mkutmonadded missing metabolite identifiers
89803view11:37, 6 October 2016Mkutmonfixed special characters in description
87427view11:51, 22 July 2016MkutmonModified description
86036view12:36, 28 June 2016EveloModified title
79953view11:49, 28 April 2015ZariAnnotated IP3 and IKK
79265view20:25, 19 March 2015ZariChenged Identifier for NFC1
71549view19:25, 17 October 2013MaintBotremoved data source from nodes without identifier
71001view15:55, 22 September 2013EgonwAdded three metabolite IDs.
67076view10:03, 26 June 2013Christine ChichesterOntology Term : 'brain-derived neurotrophic factor signaling pathway' added !
61289view21:55, 6 April 2013MaintBotremoved old publication references
61232view17:23, 5 April 2013MaintBotupdated pathway elements from provided gpml
61042view04:48, 3 April 2013NetPathModified description
60957view10:30, 1 April 2013NetPathPeriodical save, work in progress
54595view18:45, 4 December 2012MaintBotModified categories
54573view07:11, 4 December 2012NetPathModified description
54552view13:14, 3 December 2012NetPathNew pathway

External references


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NameTypeDatabase referenceComment
ACACBProtein32 (Entrez Gene)
ADAM17Protein6868 (Entrez Gene)
AKT1Protein207 (Entrez Gene)
ALPLRna249 (Entrez Gene)
APCProtein324 (Entrez Gene)
BADProtein572 (Entrez Gene)
BCL2L11Rna10018 (Entrez Gene)
BDNFRna627 (Entrez Gene)
BMP2Rna650 (Entrez Gene)
CAMK1Protein8536 (Entrez Gene)
CAMK2Protein815 (Entrez Gene)
CAMK4Protein814 (Entrez Gene)
CASP3Protein836 (Entrez Gene)
CDC42Protein998 (Entrez Gene)
CDH2Protein1000 (Entrez Gene)
CDK5Protein1020 (Entrez Gene)
CDK5R1Protein8851 (Entrez Gene)
CDKL5Protein6792 (Entrez Gene)
CEBPBProtein1385 (Entrez Gene)
CFL1Protein1072 (Entrez Gene)
CNR1Protein1268 (Entrez Gene)
CREB1Protein1385 (Entrez Gene)
CRTC1Protein23373 (Entrez Gene)
CSNK2A1Protein1457 (Entrez Gene)
CTNNB1Protein1499 (Entrez Gene)
CYFIP1GeneProduct23191 (Entrez Gene)
DAGMetaboliteCHEBI:18035 (ChEBI)
DLG1Protein1739 (Entrez Gene)
DOCK3Protein1795 (Entrez Gene)
DOK5Protein55816 (Entrez Gene)
DPYSL2Protein1808 (Entrez Gene)
EEF2Protein1938 (Entrez Gene)
EGR1Rna1958 (Entrez Gene)
EGR2Rna1959 (Entrez Gene)
EIF2S1Protein1965 (Entrez Gene)
EIF2S2Protein8894 (Entrez Gene)
EIF4EProtein1977 (Entrez Gene)
EIF4EBP1Protein1978 (Entrez Gene)
ELK1Protein2002 (Entrez Gene)
FOSRna2353 (Entrez Gene)
FOXO3Protein2309 (Entrez Gene)
FRS2Protein10818 (Entrez Gene)
FRS3Protein10817 (Entrez Gene)
FYNProtein2534 (Entrez Gene)
GABRB3Protein2562 (Entrez Gene)
GNB2L1Protein10399 (Entrez Gene)
GRB2Protein2885 (Entrez Gene)
GRIA1Protein2890 (Entrez Gene)
GRIA2Protein2891 (Entrez Gene)
GRIA3Protein2892 (Entrez Gene)
GRIN1Protein2902 (Entrez Gene)
GRIN2BProtein2904 (Entrez Gene)
GRIP1Protein23426 (Entrez Gene)
GSK3BProtein2932 (Entrez Gene)
HRASProtein3265 (Entrez Gene)
IGF2BP1Protein10642 (Entrez Gene)
IKK1GeneProduct1147 (Entrez Gene)
IKK2GeneProduct3551 (Entrez Gene)
IP3MetaboliteHMDB0001143 (HMDB)
IRS1Protein3667 (Entrez Gene)
IRS2Protein8660 (Entrez Gene)
IkkGGeneProduct8517 (Entrez Gene)
JAK2Protein3717 (Entrez Gene)
JUNProtein3725 (Entrez Gene)
KCNA3Protein3738 (Entrez Gene)
KCNN2Protein3781 (Entrez Gene)
KIDINS220Protein57498 (Entrez Gene)
KSR1Protein8844 (Entrez Gene)
LINGO1Protein84894 (Entrez Gene)
MAP2K1Protein5604 (Entrez Gene)
MAP2K2Protein5605 (Entrez Gene)
MAP2K5Protein5607 (Entrez Gene)
MAP3K1Protein4214 (Entrez Gene)
MAP3K2Protein10746 (Entrez Gene)
MAPK10Protein5602 (Entrez Gene)
MAPK14Protein1432 (Entrez Gene)
MAPK1Protein5594 (Entrez Gene)
MAPK3Protein5595 (Entrez Gene)
MAPK7Protein5598 (Entrez Gene)
MAPK8Protein5599 (Entrez Gene)
MAPK9Protein5601 (Entrez Gene)
MAPTProtein4137 (Entrez Gene)
MARCKSProtein4082 (Entrez Gene)
MEF2AProtein4205 (Entrez Gene)
MEF2CProtein4208 (Entrez Gene)
MTORProtein2475 (Entrez Gene)
NCAM1Protein4684 (Entrez Gene)
NCF1Protein653361 (Entrez Gene)
NCF2Protein4688 (Entrez Gene)
NCK1Protein4690 (Entrez Gene)
NCK2Protein8440 (Entrez Gene)
NFATC4Protein4776 (Entrez Gene)
NFKB1Protein4790 (Entrez Gene)
NFKBIAProtein4792 (Entrez Gene)
NGFProtein4803 (Entrez Gene)
NGFRProtein4804 (Entrez Gene)
NSFProtein4905 (Entrez Gene)
NTF3Protein4908 (Entrez Gene)
NTRK1Protein4914 (Entrez Gene)
NTRK2Protein4915 (Entrez Gene)
NTRK3Protein4916 (Entrez Gene)
PDPK1Protein5170 (Entrez Gene)
PIK3CAProtein5296 (Entrez Gene)
PIK3R1Protein5295 (Entrez Gene)
PIK3R2Protein5296 (Entrez Gene)
PIP2MetaboliteQ3083814 (Wikidata)
PIP3MetaboliteCHEBI:16618 (ChEBI)
PLCG1Protein5335 (Entrez Gene)
PPP2CAProtein5515 (Entrez Gene)
PRKAA1Protein5562 (Entrez Gene)
PRKAA2Protein5563 (Entrez Gene)
PRKCDProtein5580 (Entrez Gene)
PTK2BProtein2185 (Entrez Gene)
PTPN11Protein5781 (Entrez Gene)
PTPRFProtein5792 (Entrez Gene)
RAB3AProtein5864 (Entrez Gene)
RAC1Protein5879 (Entrez Gene)
RAF1Protein5894 (Entrez Gene)
RANBP9Protein10048 (Entrez Gene)
RAP1AProtein5906 (Entrez Gene)
RASGRF1Protein5923 (Entrez Gene)
RELAProtein5970 (Entrez Gene)
RHOGProtein391 (Entrez Gene)
RPS6Protein6194 (Entrez Gene)
RPS6KA1Protein6195 (Entrez Gene)
RPS6KA3Protein6197 (Entrez Gene)
RPS6KA5Protein9252 (Entrez Gene)
RPS6KB1Protein6198 (Entrez Gene)
SH2B2Protein10603 (Entrez Gene)
SH2BProtein25970 (Entrez Gene)
SHC1Protein6464 (Entrez Gene)
SHC2Protein25759 (Entrez Gene)
SHC3Protein53358 (Entrez Gene)
SHC4Protein399694 (Entrez Gene)
SIRPAProtein140885 (Entrez Gene)
SORT1Protein6272 (Entrez Gene)
SPP1Rna6696 (Entrez Gene)
SQSTM1Protein8878 (Entrez Gene)
SRCProtein6714 (Entrez Gene)
STAT1Protein6772 (Entrez Gene)
STAT3Protein6774 (Entrez Gene)
STAT5AProtein6776 (Entrez Gene)
STAT5BProtein6777 (Entrez Gene)
SYN1Protein6853 (Entrez Gene)
TIAM1Protein7074 (Entrez Gene)
TRAF6Protein7189 (Entrez Gene)
TSC2Protein7249 (Entrez Gene)
VAV2Protein7410 (Entrez Gene)
VAV3Protein10451 (Entrez Gene)
YBX1Protein4904 (Entrez Gene)
cAMPMetaboliteCHEBI:17489 (ChEBI)

Annotated Interactions

No annotated interactions