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Biochemical and functional interactions between the neurotrophin receptors trk and p75 NTR
Author(s) -
Bibel Miriam,
Hoppe Edmund,
Barde YvesAlain
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.3.616
Subject(s) - trk receptor , tropomyosin receptor kinase b , tropomyosin receptor kinase a , low affinity nerve growth factor receptor , neurotrophin , biology , tropomyosin receptor kinase c , microbiology and biotechnology , receptor , nerve growth factor , neurotrophic factors , biochemistry , platelet derived growth factor receptor , growth factor
Neurotrophins bind to two structurally unrelated receptors, the trk tyrosine kinases and the neurotrophin receptor p75 NTR . Ligand activation of these two types of receptor can lead to opposite actions, in particular the prevention or activation of programmed cell death. Many cells co‐express trk receptors and p75 NTR , and we found that p75 NTR was co‐precipitated with trk A, trk B and trk C in cells transfected with both receptor types. Co‐precipitation of p75 NTR was not observed with the epidermal growth factor receptor. Experiments with deletion constructs of trk B (the most abundant trk receptor in the brain) and p75 NTR revealed that both the extracellular and intracellular domains of trk B and p75 NTR contribute to the interaction. Blocking autophosphorylation of trk B substantially reduced the interactions between p75 NTR and trk B constructs containing the intracellular, but not the extracellular, domains. We also found that co‐expression of p75 NTR with trk B resulted in a clear increase in the specificity of trk B activation by brain‐derived neurotrophic factor, compared with neurotrophin‐3 and neurotrophin‐4/5. These results indicate a close proximity of the two neurotrophin receptors within cell membranes, and suggest that the signalling pathways they initiate may interact soon after their activation.