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p75 NTR receptor-mediated signalling
Stable Identifier
R-HSA-193704
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Signal Transduction (Homo sapiens)
Death Receptor Signaling (Homo sapiens)
p75 NTR receptor-mediated signalling (Homo sapiens)
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Besides signalling through the tyrosine kinase receptors TRK A, B, and C, the mature neurotrophins NGF, BDNF, and NT3/4 signal through their common receptor p75NTR. NGF binding to p75NTR activates a number of downstream signalling events controlling survival, death, proliferation, and axonogenesis, according to the cellular context. p75NTR is devoid of enzymatic activity, and signals by recruiting other proteins to its own intracellular domain. p75 interacting proteins include NRIF, TRAF2, 4, and 6, NRAGE, necdin, SC1, NADE, RhoA, Rac, ARMS, RIP2, FAP and PLAIDD. Here we annotate only the proteins for which a clear involvement in p75NTR signalling was demonstrated.
A peculiarity of p75NTR is the ability to bind the pro-neurotrophins proNGF and proBDNF. Proneurotrophins do not associate with TRK receptors, whereas they efficiently signal cell death by apoptosis through p75NTR. The biological action of neurotrophins is thus regulated by proteolytic cleavage, with proforms preferentially activating p75NTR, mediating apoptosis, and mature forms activating TRK receptors, to promote survival. Moreover, the two receptors are utilised to differentially modulate neuronal plasticity. For instance, proBDNF-p75NTR signalling facilitates LTD, long term depression, in the hippocampus (Woo NH, et al, 2005), while BDNF-TRKB signalling promotes LTP (long term potentiation). Many biological observations indicate a functional interaction between p75NTR and TRKA signaling pathways.
Literature References
PubMed ID
Title
Journal
Year
16699811
Neurotrophin signaling: many exciting surprises!
Arevalo, JC
,
Wu, SH
Cell Mol Life Sci
2006
16939974
Neurotrophin-regulated signalling pathways
Reichardt, LF
Philos Trans R Soc Lond B Biol Sci
2006
12671646
Neurotrophins and their receptors: a convergence point for many signalling pathways
Chao, MV
Nat Rev Neurosci
2003
Participants
Events
NFG and proNGF binds to p75NTR
(Homo sapiens)
Cell death signalling via NRAGE, NRIF and NADE
(Homo sapiens)
p75NTR negatively regulates cell cycle via SC1
(Homo sapiens)
p75NTR signals via NF-kB
(Homo sapiens)
Ceramide signalling
(Homo sapiens)
p75NTR regulates axonogenesis
(Homo sapiens)
Regulated proteolysis of p75NTR
(Homo sapiens)
Participates
as an event of
Death Receptor Signaling (Homo sapiens)
Event Information
Go Biological Process
neurotrophin TRK receptor signaling pathway (0048011)
Orthologous Events
p75 NTR receptor-mediated signalling (Bos taurus)
p75 NTR receptor-mediated signalling (Caenorhabditis elegans)
p75 NTR receptor-mediated signalling (Canis familiaris)
p75 NTR receptor-mediated signalling (Danio rerio)
p75 NTR receptor-mediated signalling (Dictyostelium discoideum)
p75 NTR receptor-mediated signalling (Drosophila melanogaster)
p75 NTR receptor-mediated signalling (Gallus gallus)
p75 NTR receptor-mediated signalling (Mus musculus)
p75 NTR receptor-mediated signalling (Rattus norvegicus)
p75 NTR receptor-mediated signalling (Saccharomyces cerevisiae)
p75 NTR receptor-mediated signalling (Schizosaccharomyces pombe)
p75 NTR receptor-mediated signalling (Sus scrofa)
p75 NTR receptor-mediated signalling (Xenopus tropicalis)
Authored
Nasi, S (2006-10-10)
Annibali, D (2006-10-10)
Reviewed
Friedman, WJ (2008-05-20)
Chao, MV (2008-05-28)
Created
Jassal, B (2007-02-23)
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