WP5539 (Homo sapiens)

From WikiPathways

Revision as of 15:13, 22 July 2025 by Khanspers (Talk | contribs)
(diff) ←Older revision | Current revision (diff) | Newer revision→ (diff)
Jump to: navigation, search


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.

Try the New WikiPathways

View approved pathways at the new wikipathways.org.

Quality Tags

Ontology Terms

 

Bibliography

View all...
  1. Lee R, Kermani P, Teng KK, Hempstead BL; ''Regulation of cell survival by secreted proneurotrophins.''; Science, 2001 PubMed Europe PMC Scholia
  2. Schwamborn JC, Püschel AW; ''The sequential activity of the GTPases Rap1B and Cdc42 determines neuronal polarity.''; Nat Neurosci, 2004 PubMed Europe PMC Scholia
  3. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM; ''Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex.''; Science, 2005 PubMed Europe PMC Scholia
  4. Nishimura T, Yamaguchi T, Kato K, Yoshizawa M, Nabeshima Y, Ohno S, Hoshino M, Kaibuchi K; ''PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1.''; Nat Cell Biol, 2005 PubMed Europe PMC Scholia
  5. Besset V, Scott RP, Ibáñez CF; ''Signaling complexes and protein-protein interactions involved in the activation of the Ras and phosphatidylinositol 3-kinase pathways by the c-Ret receptor tyrosine kinase.''; J Biol Chem, 2000 PubMed Europe PMC Scholia
  6. Litosch I; ''Regulating G protein activity by lipase-independent functions of phospholipase C.''; Life Sci, 2015 PubMed Europe PMC Scholia
  7. Liu J, Xiao Q, Xiao J, Niu C, Li Y, Zhang X, Zhou Z, Shu G, Yin G; ''Wnt/β-catenin signalling: function, biological mechanisms, and therapeutic opportunities.''; Signal Transduct Target Ther, 2022 PubMed Europe PMC Scholia
  8. Katoh M; ''Cross-talk of WNT and FGF signaling pathways at GSK3beta to regulate beta-catenin and SNAIL signaling cascades.''; Cancer Biol Ther, 2006 PubMed Europe PMC Scholia
  9. Dobrowsky RT, Werner MH, Castellino AM, Chao MV, Hannun YA; ''Activation of the sphingomyelin cycle through the low-affinity neurotrophin receptor.''; Science, 1994 PubMed Europe PMC Scholia
  10. Yamada M, Ohnishi H, Sano Si, Nakatani A, Ikeuchi T, Hatanaka H; ''Insulin receptor substrate (IRS)-1 and IRS-2 are tyrosine-phosphorylated and associated with phosphatidylinositol 3-kinase in response to brain-derived neurotrophic factor in cultured cerebral cortical neurons.''; J Biol Chem, 1997 PubMed Europe PMC Scholia
  11. Ng J, Luo L; ''Rho GTPases regulate axon growth through convergent and divergent signaling pathways.''; Neuron, 2004 PubMed Europe PMC Scholia
  12. Kanamoto T, Mota M, Takeda K, Rubin LL, Miyazono K, Ichijo H, Bazenet CE; ''Role of apoptosis signal-regulating kinase in regulation of the c-Jun N-terminal kinase pathway and apoptosis in sympathetic neurons.''; Mol Cell Biol, 2000 PubMed Europe PMC Scholia
  13. Kishida S, Koyama S, Matsubara K, Kishida M, Matsuura Y, Kikuchi A; ''''; , PubMed Europe PMC Scholia
  14. Yamashita T, Fujitani M, Hata K, Mimura F, Yamagishi S; ''Diverse functions of the p75 neurotrophin receptor.''; Anat Sci Int, 2005 PubMed Europe PMC Scholia
  15. Wang D, Liu G, Meng Y, Chen H, Ye Z, Jing J; ''The Configuration of GRB2 in Protein Interaction and Signal Transduction.''; Biomolecules, 2024 PubMed Europe PMC Scholia
  16. Pramanik S, Sulistio YA, Heese K; ''Neurotrophin Signaling and Stem Cells-Implications for Neurodegenerative Diseases and Stem Cell Therapy.''; Mol Neurobiol, 2017 PubMed Europe PMC Scholia
  17. Chen C, Wirth A, Ponimaskin E; ''Cdc42: an important regulator of neuronal morphology.''; Int J Biochem Cell Biol, 2012 PubMed Europe PMC Scholia
  18. Leal G, Comprido D, Duarte CB; ''BDNF-induced local protein synthesis and synaptic plasticity.''; Neuropharmacology, 2014 PubMed Europe PMC Scholia
  19. Yang JW, Ma W, Luo T, Wang DY, Lu JJ, Li XT, Wang TT, Cheng JR, Ru J, Gao Y, Liu J, Liang Z, Yang ZY, Dai P, He YS, Guo XB, Guo JH, Li LY; ''BDNF promotes human neural stem cell growth via GSK-3β-mediated crosstalk with the wnt/β-catenin signaling pathway.''; Growth Factors, 2016 PubMed Europe PMC Scholia
  20. Heinrich JN, Kwak SP, Howland DS, Chen J, Sturner S, Sullivan K, Lipinski K, Cheng KY, She Y, Lo F, Ghavami A; ''Disruption of ShcA signaling halts cell proliferation--characterization of ShcC residues that influence signaling pathways using yeast.''; Cell Signal, 2006 PubMed Europe PMC Scholia
  21. Easton JB, Moody NM, Zhu X, Middlemas DS; ''Brain-derived neurotrophic factor induces phosphorylation of fibroblast growth factor receptor substrate 2.''; J Biol Chem, 1999 PubMed Europe PMC Scholia
  22. Reichardt LF; ''Neurotrophin-regulated signalling pathways.''; Philos Trans R Soc Lond B Biol Sci, 2006 PubMed Europe PMC Scholia
  23. Hale, VA; ''The role of NFicB-dependent gene expression in regulating the growth of developing peripheral neurons''; , 2006
  24. Hofer F, Fields S, Schneider C, Martin GS; ''Activated Ras interacts with the Ral guanine nucleotide dissociation stimulator.''; Proc Natl Acad Sci U S A, 1994 PubMed Europe PMC Scholia
  25. Meakin SO, MacDonald JI, Gryz EA, Kubu CJ, Verdi JM; ''''; , PubMed Europe PMC Scholia
  26. Roux PP, Barker PA; ''''; , PubMed Europe PMC Scholia
  27. Huang EJ, Reichardt LF; ''''; , PubMed Europe PMC Scholia
  28. Schwartz M; ''Rho signalling at a glance.''; J Cell Sci, 2004 PubMed Europe PMC Scholia
  29. Watabe-Uchida M, John KA, Janas JA, Newey SE, Van Aelst L; ''The Rac activator DOCK7 regulates neuronal polarity through local phosphorylation of stathmin/Op18.''; Neuron, 2006 PubMed Europe PMC Scholia
  30. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME; ''''; , PubMed Europe PMC Scholia
  31. Huang EJ, Reichardt LF; ''''; , PubMed Europe PMC Scholia
  32. English J, Pearson G, Wilsbacher J, Swantek J, Karandikar M, Xu S, Cobb MH; ''New insights into the control of MAP kinase pathways.''; Exp Cell Res, 1999 PubMed Europe PMC Scholia
  33. Patapoutian A, Reichardt LF; ''Trk receptors: mediators of neurotrophin action.''; Curr Opin Neurobiol, 2001 PubMed Europe PMC Scholia
  34. Shepherd TR, Hard RL, Murray AM, Pei D, Fuentes EJ; ''Distinct ligand specificity of the Tiam1 and Tiam2 PDZ domains.''; Biochemistry, 2011 PubMed Europe PMC Scholia
  35. Qian X, Riccio A, Zhang Y, Ginty DD; ''Identification and characterization of novel substrates of Trk receptors in developing neurons.''; Neuron, 1998 PubMed Europe PMC Scholia
  36. Strohmaier C, Carter BD, Urfer R, Barde YA, Dechant G; ''A splice variant of the neurotrophin receptor trkB with increased specificity for brain-derived neurotrophic factor.''; EMBO J, 1996 PubMed Europe PMC Scholia
  37. Rivera C, Voipio J, Thomas-Crusells J, Li H, Emri Z, Sipilä S, Payne JA, Minichiello L, Saarma M, Kaila K; ''''; , PubMed Europe PMC Scholia
  38. Jaudon F, Albini M, Ferroni S, Benfenati F, Cesca F; ''A developmental stage- and Kidins220-dependent switch in astrocyte responsiveness to brain-derived neurotrophic factor.''; J Cell Sci, 2021 PubMed Europe PMC Scholia
  39. Feng D, Kim T, Ozkan E, Light M, Torkin R, Teng KK, Hempstead BL, Garcia KC; ''Molecular and structural insight into proNGF engagement of p75NTR and sortilin.''; J Mol Biol, 2010 PubMed Europe PMC Scholia

History

CompareRevisionActionTimeUserComment
140079view15:13, 22 July 2025KhanspersModified title
139031view13:12, 12 May 2025Qiushantaly RosinaModified title
138858view07:25, 6 May 2025Qiushantaly RosinaNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
14-3-3
AKT1GeneProductENSG00000142208 (Ensembl) leads to survival
APAF1GeneProductENSG00000120868 (Ensembl)
ARHGDIAGeneProductENSG00000141522 (Ensembl)
BADGeneProductENSG00000002330 (Ensembl)
BAXGeneProductENSG00000087088 (Ensembl)
BCL2GeneProductENSG00000171791 (Ensembl) survival
BCL2L11GeneProduct10018 (Entrez Gene)
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
  • Type your comment here
DOCK7GeneProductENSG00000116641 (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)
IKBKBGeneProductENSG00000104365 (Ensembl)
IKBKGGeneProductENSG00000269335 (Ensembl)
IKK GeneProduct
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)
MTORGeneProductENSG00000198793 (Ensembl)
MYCGeneProductENSG00000136997 (Ensembl) cell cycle regulation
NFKBIAGeneProductENSG00000100906 (Ensembl)
  • survival
  • retrograde transport
  • Type your comment here
NGFRGeneProductENSG00000064300 (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)
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
ceramidesMetaboliteCHEBI:17761 (ChEBI)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP5539"
Personal tools